rs556679

Variant names:

• chr6-31926578-C-T
• rs556679
• ENST00000695637.1:c.-359-1377C>T

Variant summary

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

The ENST00000695637.1(C2):​c.-359-1377C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 151,766 control chromosomes in the GnomAD database, including 866 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 0.11 (866 hom., cov: 30)
• Consequence: C2 ENST00000695637.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.427
• Publications: 3 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.119 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C2	NM_001178063.3	c.74-7032C>T		intron_variant	Intron 1 of 13		NP_001171534.1
C2	NM_001282457.2	c.-63-7032C>T		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.-359-1377C>T		intron_variant	Intron 1 of 17			ENSP00000512074.1
C2	ENST00000497706.6	c.-63-7032C>T		intron_variant	Intron 1 of 14	5		ENSP00000417482.2
C2	ENST00000452323.7	c.74-7032C>T		intron_variant	Intron 1 of 13	2		ENSP00000392322.2

Frequencies

GnomAD3 genomes AF: 0.107 AC: 16167 AN: 151658 Hom.: 864 Cov.: 30

Gnomad AFR AF: 0.121

Gnomad AMI AF: 0.0451

Gnomad AMR AF: 0.0993

Gnomad ASJ AF: 0.0605

Gnomad EAS AF: 0.0272

Gnomad SAS AF: 0.0757

Gnomad FIN AF: 0.0951

Gnomad MID AF: 0.0732

Gnomad NFE AF: 0.112

Gnomad OTH AF: 0.116

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

GnomAD4 genome AF: 0.107 AC: 16186 AN: 151766 Hom.: 866 Cov.: 30 AF XY: 0.105 AC XY: 7753 AN XY: 74164

African (AFR) AF: 0.121 AC: 5026 AN: 41370

American (AMR) AF: 0.0996 AC: 1517 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.0605 AC: 210 AN: 3472

East Asian (EAS) AF: 0.0275 AC: 142 AN: 5166

South Asian (SAS) AF: 0.0748 AC: 360 AN: 4814

European-Finnish (FIN) AF: 0.0951 AC: 996 AN: 10478

Middle Eastern (MID) AF: 0.0788 AC: 23 AN: 292

European-Non Finnish (NFE) AF: 0.112 AC: 7628 AN: 67922

Other (OTH) AF: 0.115 AC: 243 AN: 2108

Alfa AF: 0.104 Hom.: 107

Bravo AF: 0.108

Asia WGS AF: 0.0560 AC: 194 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.7
DANN	Benign	0.86
PhyloP100		-0.43
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: rs556679; hg19: chr6-31894355;