rs3020644

Variant names:

• chr6-31926849-A-G
• rs3020644
• ENST00000695637.1:c.-359-1106A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000695637.1(C2):​c.-359-1106A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.344 in 151,952 control chromosomes in the GnomAD database, including 10,635 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.34 (10635 hom., cov: 31)
• Consequence: C2 ENST00000695637.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.677
• Publications: 50 publications found

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 Gene-Disease associations (from GenCC):

• complement component 2 deficiency

  Inheritance: AR Classification: STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.557 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C2	NM_001178063.3	c.74-6761A>G		intron_variant	Intron 1 of 13		NP_001171534.1
C2	NM_001282457.2	c.-63-6761A>G		intron_variant	Intron 1 of 13		NP_001269386.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C2	ENST00000695637.1	c.-359-1106A>G		intron_variant	Intron 1 of 17			ENSP00000512074.1
C2	ENST00000497706.6	c.-63-6761A>G		intron_variant	Intron 1 of 14	5		ENSP00000417482.2
C2	ENST00000452323.7	c.74-6761A>G		intron_variant	Intron 1 of 13	2		ENSP00000392322.2

Frequencies

GnomAD3 genomes AF: 0.344 AC: 52259 AN: 151834 Hom.: 10623 Cov.: 31

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.478

Gnomad AMR AF: 0.512

Gnomad ASJ AF: 0.637

Gnomad EAS AF: 0.574

Gnomad SAS AF: 0.378

Gnomad FIN AF: 0.359

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.389

Gnomad OTH AF: 0.381

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.344 AC: 52278 AN: 151952 Hom.: 10635 Cov.: 31 AF XY: 0.347 AC XY: 25760 AN XY: 74268

African (AFR) AF: 0.141 AC: 5848 AN: 41474

American (AMR) AF: 0.513 AC: 7818 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.637 AC: 2212 AN: 3470

East Asian (EAS) AF: 0.574 AC: 2970 AN: 5174

South Asian (SAS) AF: 0.379 AC: 1822 AN: 4804

European-Finnish (FIN) AF: 0.359 AC: 3784 AN: 10528

Middle Eastern (MID) AF: 0.483 AC: 142 AN: 294

European-Non Finnish (NFE) AF: 0.389 AC: 26441 AN: 67946

Other (OTH) AF: 0.382 AC: 806 AN: 2112

Alfa AF: 0.395 Hom.: 48660

Bravo AF: 0.350

Asia WGS AF: 0.406 AC: 1415 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	5.6
DANN	Benign	0.78
PhyloP100		0.68
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs3020644; hg19: chr6-31894626;