rs547154

chr6-31943161-G-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_000063.6(C2):c.1360+62G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.1 in 1,612,262 control chromosomes in the GnomAD database, including 8,996 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as protective (no stars).

• Frequency:
  • Genomes: 𝑓 0.12 (1195 hom., cov: 31)
  • Exomes 𝑓: 0.098 (7801 hom.)
• Consequence: C2 NM_000063.6 intron
• Clinical Significance: protective no assertion criteria provided B:1
• Conservation: PhyloP100: -0.537

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 6-31943161-G-T is Benign according to our data. Variant chr6-31943161-G-T is described in ClinVar as [protective]. Clinvar id is 12131.Status of the report is no_assertion_criteria_provided, 0 stars. We mark this variant Likely_benign, oryginal submission is: [protective]. Variant chr6-31943161-G-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.187 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C2	NM_000063.6	c.1360+62G>T		intron_variant		ENST00000299367.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C2	ENST00000299367.10	c.1360+62G>T		intron_variant		1	NM_000063.6	P1

Frequencies

GnomAD3 genomes AF: 0.117 AC: 17723 AN: 151974 Hom.: 1197 Cov.: 31

Gnomad AFR AF: 0.190

Gnomad AMI AF: 0.0462

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.0571

Gnomad EAS AF: 0.0617

Gnomad SAS AF: 0.144

Gnomad FIN AF: 0.0568

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0908

Gnomad OTH AF: 0.131

GnomAD4 exome AF: 0.0982 AC: 143452 AN: 1460170 Hom.: 7801 Cov.: 33 AF XY: 0.0993 AC XY: 72139 AN XY: 726438

Gnomad4 AFR exome AF: 0.188

Gnomad4 AMR exome AF: 0.0738

Gnomad4 ASJ exome AF: 0.0555

Gnomad4 EAS exome AF: 0.0736

Gnomad4 SAS exome AF: 0.156

Gnomad4 FIN exome AF: 0.0651

Gnomad4 NFE exome AF: 0.0950

Gnomad4 OTH exome AF: 0.109

GnomAD4 genome AF: 0.117 AC: 17744 AN: 152092 Hom.: 1195 Cov.: 31 AF XY: 0.114 AC XY: 8509 AN XY: 74346

Gnomad4 AFR AF: 0.190

Gnomad4 AMR AF: 0.101

Gnomad4 ASJ AF: 0.0571

Gnomad4 EAS AF: 0.0617

Gnomad4 SAS AF: 0.143

Gnomad4 FIN AF: 0.0568

Gnomad4 NFE AF: 0.0908

Gnomad4 OTH AF: 0.130

Alfa AF: 0.0984 Hom.: 602

Bravo AF: 0.124

Asia WGS AF: 0.154 AC: 535 AN: 3478

ClinVar

Significance: protective

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

Age related macular degeneration 14 Benign:1

protective, no assertion criteria provided

literature only

OMIM

May 18, 2015

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	0.70
Dann	Benign	0.76

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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

Other links and lift over

dbSNP: rs547154; hg19: chr6-31910938; COSMIC: COSV54963335; COSMIC: COSV54963335;