rs1042663
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_000063.6(C2):c.1023G>A(p.Ala341Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0996 in 1,612,312 control chromosomes in the GnomAD database, including 8,985 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.12 ( 1220 hom., cov: 29)
Exomes 𝑓: 0.098 ( 7765 hom. )
Consequence
C2
NM_000063.6 synonymous
NM_000063.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0410
Genes affected
C2 (HGNC:1248): (complement C2) Component C2 is a serum glycoprotein that functions as part of the classical pathway of the complement system. Activated C1 cleaves C2 into C2a and C2b. The serine proteinase C2a then combines with complement factor 4b to create the C3 or C5 convertase. Deficiency of C2 has been reported to associated with certain autoimmune diseases and SNPs in this gene have been associated with altered susceptibility to age-related macular degeneration. This gene localizes within the class III region of the MHC on the short arm of chromosome 6. Alternative splicing results in multiple transcript variants encoding distinct isoforms. Additional transcript variants have been described in publications but their full-length sequence has not been determined.[provided by RefSeq, Mar 2009]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BP6
Variant 6-31937353-G-A is Benign according to our data. Variant chr6-31937353-G-A is described in ClinVar as [Benign]. Clinvar id is 356245.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-31937353-G-A is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=-0.041 with no splicing effect.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.188 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
C2 | NM_000063.6 | c.1023G>A | p.Ala341Ala | synonymous_variant | 8/18 | ENST00000299367.10 | NP_000054.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
C2 | ENST00000299367.10 | c.1023G>A | p.Ala341Ala | synonymous_variant | 8/18 | 1 | NM_000063.6 | ENSP00000299367.5 | ||
ENSG00000244255 | ENST00000456570.5 | c.564G>A | p.Ala188Ala | synonymous_variant | 5/30 | 2 | ENSP00000410815.1 |
Frequencies
GnomAD3 genomes AF: 0.117 AC: 17727AN: 151746Hom.: 1222 Cov.: 29
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GnomAD3 exomes AF: 0.0969 AC: 23910AN: 246640Hom.: 1391 AF XY: 0.0999 AC XY: 13434AN XY: 134446
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GnomAD4 exome AF: 0.0978 AC: 142895AN: 1460448Hom.: 7765 Cov.: 33 AF XY: 0.0989 AC XY: 71870AN XY: 726556
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GnomAD4 genome AF: 0.117 AC: 17747AN: 151864Hom.: 1220 Cov.: 29 AF XY: 0.115 AC XY: 8509AN XY: 74238
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ClinVar
Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 28, 2016 | 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: Frequency - |
Complement component 2 deficiency Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | 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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Age related macular degeneration 14 Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | 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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Feb 01, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at