rs550605

Variant names:

• chr6-31939370-T-C
• rs550605
• NM_000063.6:c.1219+50T>C

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.60
• Publications: 33 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]

ENSG00000244255 (HGNC:):

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

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000063.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C2	NM_000063.6	MANE Select	c.1219+50T>C		intron	N/A	NP_000054.2
	C2	NM_001282458.2		c.1132+50T>C		intron	N/A	NP_001269387.1	A0A0G2JL69
	C2	NM_001145903.3		c.823+50T>C		intron	N/A	NP_001139375.1	P06681-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C2	ENST00000299367.10	TSL:1 MANE Select	c.1219+50T>C		intron	N/A	ENSP00000299367.5	P06681-1
	ENSG00000244255	ENST00000456570.5	TSL:2	c.760+50T>C		intron	N/A	ENSP00000410815.1	B4E1Z4
	ENSG00000244255	ENST00000477310.1	TSL:5	c.673+50T>C		intron	N/A	ENSP00000418996.1	E7ETN3

Frequencies

GnomAD3 genomes AF: 0.117 AC: 17736 AN: 152022 Hom.: 1202 Cov.: 31

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

GnomAD2 exomes AF: 0.0969 AC: 23817 AN: 245758 AF XY: 0.0998

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 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.: 17 AF XY: 0.0976 AC XY: 59372 AN XY: 608086

African (AFR) AF: 0.189 AC: 5342 AN: 28292

American (AMR) AF: 0.0735 AC: 3261 AN: 44386

Ashkenazi Jewish (ASJ) AF: 0.0547 AC: 1339 AN: 24482

East Asian (EAS) AF: 0.0713 AC: 2750 AN: 38580

South Asian (SAS) AF: 0.155 AC: 12557 AN: 80808

European-Finnish (FIN) AF: 0.0648 AC: 3359 AN: 51812

Middle Eastern (MID) AF: 0.0710 AC: 283 AN: 3986

European-Non Finnish (NFE) AF: 0.0925 AC: 80696 AN: 872240

Other (OTH) AF: 0.109 AC: 5592 AN: 51492

GnomAD4 genome AF: 0.117 AC: 17757 AN: 152140 Hom.: 1200 Cov.: 31 AF XY: 0.115 AC XY: 8517 AN XY: 74382

African (AFR) AF: 0.191 AC: 7900 AN: 41462

American (AMR) AF: 0.100 AC: 1535 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0574 AC: 199 AN: 3464

East Asian (EAS) AF: 0.0587 AC: 304 AN: 5180

South Asian (SAS) AF: 0.141 AC: 679 AN: 4812

European-Finnish (FIN) AF: 0.0577 AC: 612 AN: 10602

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.0909 AC: 6182 AN: 68020

Other (OTH) AF: 0.131 AC: 276 AN: 2114

Alfa AF: 0.0978 Hom.: 2543

Bravo AF: 0.124

Asia WGS AF: 0.155 AC: 536 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.093
DANN	Benign	0.58
PhyloP100		-1.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs550605;

hg19: chr6-31907147;