chr6-31926167-G-A

Position:

• chr6-31926167-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001178063.3(C2):​c.74-7443G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.537 in 151,812 control chromosomes in the GnomAD database, including 22,472 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 0.54 (22472 hom., cov: 30)
• Consequence: C2 NM_001178063.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.359

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.674 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C2	NM_001178063.3	c.74-7443G>A		intron_variant			NP_001171534.1
C2	NM_001282457.2	c.-63-7443G>A		intron_variant			NP_001269386.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C2	ENST00000695637.1	c.-359-1788G>A		intron_variant				ENSP00000512074.1
C2	ENST00000497706.6	c.-63-7443G>A		intron_variant		5		ENSP00000417482.2
C2	ENST00000452323.7	c.74-7443G>A		intron_variant		2		ENSP00000392322.2

Frequencies

GnomAD3 genomes AF: 0.537 AC: 81460 AN: 151694 Hom.: 22448 Cov.: 30

Gnomad AFR AF: 0.532

Gnomad AMI AF: 0.504

Gnomad AMR AF: 0.685

Gnomad ASJ AF: 0.773

Gnomad EAS AF: 0.661

Gnomad SAS AF: 0.593

Gnomad FIN AF: 0.426

Gnomad MID AF: 0.684

Gnomad NFE AF: 0.497

Gnomad OTH AF: 0.581

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

GnomAD4 genome AF: 0.537 AC: 81538 AN: 151812 Hom.: 22472 Cov.: 30 AF XY: 0.539 AC XY: 39987 AN XY: 74162

Gnomad4 AFR AF: 0.532

Gnomad4 AMR AF: 0.685

Gnomad4 ASJ AF: 0.773

Gnomad4 EAS AF: 0.661

Gnomad4 SAS AF: 0.595

Gnomad4 FIN AF: 0.426

Gnomad4 NFE AF: 0.497

Gnomad4 OTH AF: 0.579

Alfa AF: 0.537 Hom.: 32971

Bravo AF: 0.557

Asia WGS AF: 0.564 AC: 1967 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.7
DANN	Benign	0.46

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2734335; hg19: chr6-31893944;