rs41307788
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 1P and 9B. PP3BP4_StrongBP6BS2
The NM_006610.4(MASP2):c.467G>A(p.Cys156Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00814 in 1,612,448 control chromosomes in the GnomAD database, including 67 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_006610.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00557 AC: 848AN: 152118Hom.: 1 Cov.: 33
GnomAD3 exomes AF: 0.00597 AC: 1484AN: 248664Hom.: 7 AF XY: 0.00652 AC XY: 880AN XY: 134972
GnomAD4 exome AF: 0.00841 AC: 12277AN: 1460212Hom.: 66 Cov.: 31 AF XY: 0.00840 AC XY: 6103AN XY: 726462
GnomAD4 genome AF: 0.00556 AC: 847AN: 152236Hom.: 1 Cov.: 33 AF XY: 0.00492 AC XY: 366AN XY: 74436
ClinVar
Submissions by phenotype
not provided Benign:3
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MASP2: BS2 -
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Immunodeficiency due to MASP-2 deficiency Uncertain:1Benign:1
The missense variant p.C156Y in MASP2 (NM_006610.4) has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The p.C156Y variant has a GnomAD frequency of 0.5878 %. There is a large physicochemical difference between cysteine and tyrosine, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. The p.C156Y missense variant is predicted to be damaging by both SIFT and PolyPhen2. The cysteine residue at codon 156 of MASP2 is conserved in all mammalian species. The nucleotide c.467 in MASP2 is predicted conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Uncertain Significance. -
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -
not specified Benign:1
Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Variant detected in unspecified number of cases with atypical hemolytic uremic syndrome (Bu 2014). MAF 1.2%. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at