ENPP1 R774C

(ENPP1 Arg774Cys)

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Edited in this revision:

Variant evidence
Computational	-

Functional	-

Case/Control	-1	No statistically significant data supports a pathogenic effect, and 5% allele frequency contradicts a highly penetrant effect. See Lorenz-Depiereux B et al. 2010 (20137773).

Familial		No significant familial data.
		No significant familial data.

Clinical importance
Severity	4	Potentially lethal, variable onsets reported. See Lorenz-Depiereux B et al. 2010 (20137773).

Treatability	3

Penetrance	3	Initial report suggested highly penetrant effect, but this is contradicted by a relatively high 5% allele frequency.

Moderate clinical importance, Uncertain pathogenic

(The "moderate clinical importance, uncertain" qualifier is assigned automatically based on the above evidence and importance scores.)

recessive

dbSNP reports that this variant has 5% allele frequency in a 120 chromosome low-coverage CEU panel (1000 genomes) and 2.6% in a mixed panel of Caucasian & African American samples. Lorenz-Depiereux et al. point to this as suggesting that the variant is a not causal.

http://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=28933977

The predicted incidence of homozygotes (1 in 400) vs. the incidence of the disease (quite rare) implies that this variant is a highly penetrant causal variant. It may have a modifier or susceptibility effect though (note that the son of the reported family in Lorenz-Depiereux et al. & Rutsch et al. had a more severe effect compared to his father).

Allele frequency

T @ chr6:132206079: 2.6% (278/10758) in EVS
Frequency shown in summary reports: 2.6% (278/10758)

Publications

The footnote to Table 3 states: “The mutation reported in this paper (c.2320C>T [p.Arg774Cys]) has since been shown to be a polymorphism (rs28933977) with a minor allele frequency of 5%.”

Genomes

Other external references

OMIM

Arterial calcification, generalized, of infancy
www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=173335

PolyPhen-2

Score: 0.746 (possibly damaging)

Other in silico analyses

NBLOSUM100 score = 8
GET-Evidence autoscore = 3

Edit history

Nov 29 2012 Genome Importing Robot added CGI sample GS01175-DNA_B05 from PGP sample 83494370 view
Nov 29 2012 Genome Importing Robot added CGI sample GS01173-DNA_F06 from PGP sample 64191565 view
Jun 22 2011 Genome Importing Robot added PGP13 (hu3A8D13) build 37, from CGI var (software ver 1.11.0.16) view
May 2 2011 Madeleine Ball edited article 12881724 summary view
May 2 2011 Madeleine Ball edited variant summary view
May 2 2011 Madeleine Ball edited variant summary view
May 2 2011 Madeleine Ball edited article 12881724 summary view
May 2 2011 Madeleine Ball edited article 20137773 summary view
May 2 2011 Madeleine Ball edited variant summary view
May 2 2011 Madeleine Ball added article 12881724 view
May 2 2011 Madeleine Ball edited article 20137773 summary view
May 2 2011 Madeleine Ball edited variant summary view
May 2 2011 Madeleine Ball added article 20137773 view
Jan 5 2010 OMIM Importing Robot edited variant summary view
Jan 5 2010 OMIM Importing Robot added variant view

ENPP1 R774C - GET-Evidence