dbSNP rs550605: C2:c.1219+50T>C (chr6-31939370-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000063.6(C2):c.1219+50T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0986 in 1,348,218 control chromosomes in the GnomAD database, including 7,578 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 0.12 ( 1200 hom., cov: 31)

Exomes 𝑓: 0.096 ( 6378 hom. )

Consequence

C2
NM_000063.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.60

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:

C2-AS1 (HGNC:49464): (C2 antisense RNA 1)

C2-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

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 rank	MANE	Protein	UniProt
C2	NM_000063.6 link	c.1219+50T>C		intron_variant	Intron 9 of 17	ENST00000299367.10	NP_000054.2	P06681-1Q5JP69Q53HP3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C2	ENST00000299367.10 link	c.1219+50T>C		intron_variant	Intron 9 of 17	1	NM_000063.6	ENSP00000299367.5		P06681-1
ENSG00000244255	ENST00000456570.5 link	c.760+50T>C		intron_variant	Intron 6 of 29	2		ENSP00000410815.1		B4E1Z4

Frequencies

GnomAD3 genomes

AF:

0.117

AC:

17736

AN:

152022

Hom.:

1202

Cov.:

show subpopulations

Gnomad AFR

AF:

0.190

Gnomad AMI

AF:

0.0461

Gnomad AMR

AF:

0.101

Gnomad ASJ

AF:

0.0574

Gnomad EAS

AF:

0.0587

Gnomad SAS

AF:

0.143

Gnomad FIN

AF:

0.0577

Gnomad MID

AF:

0.0886

Gnomad NFE

AF:

0.0909

Gnomad OTH

AF:

0.131

GnomAD3 exomes

AF:

0.0969

AC:

23817

AN:

245758

Hom.:

1378

AF XY:

0.0998

AC XY:

13376

AN XY:

134016

show subpopulations

Gnomad AFR exome

AF:

0.191

Gnomad AMR exome

AF:

0.0704

Gnomad ASJ exome

AF:

0.0523

Gnomad EAS exome

AF:

0.0590

Gnomad SAS exome

AF:

0.162

Gnomad FIN exome

AF:

0.0628

Gnomad NFE exome

AF:

0.0908

Gnomad OTH exome

AF:

0.103

GnomAD4 exome

AF:

0.0963

AC:

115179

AN:

1196078

Hom.:

6378

Cov.:

AF XY:

0.0976

AC XY:

59372

AN XY:

608086

show subpopulations

Gnomad4 AFR exome

AF:

0.189

Gnomad4 AMR exome

AF:

0.0735

Gnomad4 ASJ exome

AF:

0.0547

Gnomad4 EAS exome

AF:

0.0713

Gnomad4 SAS exome

AF:

0.155

Gnomad4 FIN exome

AF:

0.0648

Gnomad4 NFE exome

AF:

0.0925

Gnomad4 OTH exome

AF:

0.109

GnomAD4 genome

AF:

0.117

AC:

17757

AN:

152140

Hom.:

1200

Cov.:

AF XY:

0.115

AC XY:

8517

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.191

Gnomad4 AMR

AF:

0.100

Gnomad4 ASJ

AF:

0.0574

Gnomad4 EAS

AF:

0.0587

Gnomad4 SAS

AF:

0.141

Gnomad4 FIN

AF:

0.0577

Gnomad4 NFE

AF:

0.0909

Gnomad4 OTH

AF:

0.131

Alfa

AF:

0.0948

Hom.:

869

Bravo

AF:

0.124

Asia WGS

AF:

0.155

AC:

536

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.093

DANN

Benign

0.58

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over