rs1042663

Positions:

chr6-31937353-G-A

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.0410

Variant links:

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]

C2 links:

ENSG00000244255 (HGNC:):

ENSG00000244255 links:

Genome browser will be placed here

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 linkuse as main transcript	c.1023G>A	p.Ala341Ala	synonymous_variant	8/18	ENST00000299367.10	NP_000054.2	P06681-1Q5JP69Q53HP3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C2	ENST00000299367.10 linkuse as main transcript	c.1023G>A	p.Ala341Ala	synonymous_variant	8/18	1	NM_000063.6	ENSP00000299367.5		P06681-1
ENSG00000244255	ENST00000456570.5 linkuse as main transcript	c.564G>A	p.Ala188Ala	synonymous_variant	5/30	2		ENSP00000410815.1		B4E1Z4

Frequencies

GnomAD3 genomes

AF:

0.117

AC:

17727

AN:

151746

Hom.:

1222

Cov.:

show subpopulations

Gnomad AFR

AF:

0.191

Gnomad AMI

AF:

0.0462

Gnomad AMR

AF:

0.101

Gnomad ASJ

AF:

0.0574

Gnomad EAS

AF:

0.0589

Gnomad SAS

AF:

0.142

Gnomad FIN

AF:

0.0577

Gnomad MID

AF:

0.0886

Gnomad NFE

AF:

0.0908

Gnomad OTH

AF:

0.131

GnomAD3 exomes

AF:

0.0969

AC:

23910

AN:

246640

Hom.:

1391

AF XY:

0.0999

AC XY:

13434

AN XY:

134446

show subpopulations

Gnomad AFR exome

AF:

0.191

Gnomad AMR exome

AF:

0.0704

Gnomad ASJ exome

AF:

0.0522

Gnomad EAS exome

AF:

0.0591

Gnomad SAS exome

AF:

0.162

Gnomad FIN exome

AF:

0.0636

Gnomad NFE exome

AF:

0.0908

Gnomad OTH exome

AF:

0.103

GnomAD4 exome

AF:

0.0978

AC:

142895

AN:

1460448

Hom.:

7765

Cov.:

AF XY:

0.0989

AC XY:

71870

AN XY:

726556

show subpopulations

Gnomad4 AFR exome

AF:

0.188

Gnomad4 AMR exome

AF:

0.0739

Gnomad4 ASJ exome

AF:

0.0555

Gnomad4 EAS exome

AF:

0.0713

Gnomad4 SAS exome

AF:

0.156

Gnomad4 FIN exome

AF:

0.0651

Gnomad4 NFE exome

AF:

0.0946

Gnomad4 OTH exome

AF:

0.109

GnomAD4 genome

AF:

0.117

AC:

17747

AN:

151864

Hom.:

1220

Cov.:

AF XY:

0.115

AC XY:

8509

AN XY:

74238

show subpopulations

Gnomad4 AFR

AF:

0.191

Gnomad4 AMR

AF:

0.100

Gnomad4 ASJ

AF:

0.0574

Gnomad4 EAS

AF:

0.0589

Gnomad4 SAS

AF:

0.141

Gnomad4 FIN

AF:

0.0577

Gnomad4 NFE

AF:

0.0908

Gnomad4 OTH

AF:

0.130

Alfa

AF:

0.0920

Hom.:

1604

Bravo

AF:

0.123

Asia WGS

AF:

0.155

AC:

536

AN:

3478

EpiCase

AF:

0.0869

EpiControl

AF:

0.0884

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

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

9.5

DANN

Benign

0.41

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over