rs511294

Positions:

• chr6-31921092-T-G

Variant summary

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

The ENST00000695637.1(C2):​c.-359-6863T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0718 in 152,222 control chromosomes in the GnomAD database, including 417 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 0.072 (417 hom., cov: 32)
• Consequence: C2 ENST00000695637.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.472

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=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C2	NM_001178063.3	c.74-12518T>G		intron_variant			NP_001171534.1
C2	NM_001282457.2	c.-63-12518T>G		intron_variant			NP_001269386.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C2	ENST00000413154.5	c.-100+1066T>G		intron_variant		4		ENSP00000403325
C2	ENST00000452202.5	c.74-12518T>G		intron_variant		4		ENSP00000406121
C2	ENST00000452323.7	c.74-12518T>G		intron_variant		2		ENSP00000392322

Frequencies

GnomAD3 genomes AF: 0.0718 AC: 10921 AN: 152104 Hom.: 416 Cov.: 32

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.0318

Gnomad AMR AF: 0.0734

Gnomad ASJ AF: 0.0354

Gnomad EAS AF: 0.00501

Gnomad SAS AF: 0.0197

Gnomad FIN AF: 0.0394

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0661

Gnomad OTH AF: 0.0805

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

GnomAD4 genome AF: 0.0718 AC: 10933 AN: 152222 Hom.: 417 Cov.: 32 AF XY: 0.0690 AC XY: 5134 AN XY: 74432

Gnomad4 AFR AF: 0.107

Gnomad4 AMR AF: 0.0734

Gnomad4 ASJ AF: 0.0354

Gnomad4 EAS AF: 0.00502

Gnomad4 SAS AF: 0.0193

Gnomad4 FIN AF: 0.0394

Gnomad4 NFE AF: 0.0661

Gnomad4 OTH AF: 0.0796

Alfa AF: 0.0580 Hom.: 511

Bravo AF: 0.0774

Asia WGS AF: 0.0150 AC: 51 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.5
DANN	Benign	0.81

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs511294; hg19: chr6-31888869;