ENST00000695637.1:c.-359-12053C>T

Variant names:

• chr6-31915902-C-T
• rs9267673
• ENST00000695637.1:c.-359-12053C>T

Variant summary

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

The ENST00000695637.1(C2):​c.-359-12053C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 152,254 control chromosomes in the GnomAD database, including 1,313 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 (1313 hom., cov: 32)
• Consequence: C2 ENST00000695637.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.756
• Publications: 46 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]

C2 Gene-Disease associations (from GenCC):

• complement component 2 deficiency

  Inheritance: AR Classification: STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.185 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000695637.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C2	NM_001178063.3		c.73+14763C>T		intron	N/A	NP_001171534.1
	C2	NM_001282457.2		c.-63-17708C>T		intron	N/A	NP_001269386.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C2	ENST00000695637.1		c.-359-12053C>T		intron	N/A	ENSP00000512074.1
	C2	ENST00000497706.6	TSL:5	c.-63-17708C>T		intron	N/A	ENSP00000417482.2
	C2	ENST00000452323.7	TSL:2	c.73+14763C>T		intron	N/A	ENSP00000392322.2

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18158 AN: 152136 Hom.: 1313 Cov.: 32

Gnomad AFR AF: 0.189

Gnomad AMI AF: 0.217

Gnomad AMR AF: 0.0848

Gnomad ASJ AF: 0.0844

Gnomad EAS AF: 0.0948

Gnomad SAS AF: 0.193

Gnomad FIN AF: 0.0533

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.0921

Gnomad OTH AF: 0.125

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

GnomAD4 genome AF: 0.119 AC: 18179 AN: 152254 Hom.: 1313 Cov.: 32 AF XY: 0.119 AC XY: 8841 AN XY: 74448

African (AFR) AF: 0.189 AC: 7832 AN: 41534

American (AMR) AF: 0.0847 AC: 1295 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0844 AC: 293 AN: 3470

East Asian (EAS) AF: 0.0954 AC: 494 AN: 5176

South Asian (SAS) AF: 0.192 AC: 928 AN: 4826

European-Finnish (FIN) AF: 0.0533 AC: 566 AN: 10622

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.0921 AC: 6264 AN: 68020

Other (OTH) AF: 0.130 AC: 274 AN: 2112

Alfa AF: 0.0997 Hom.: 3311

Bravo AF: 0.123

Asia WGS AF: 0.189 AC: 657 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.62
DANN	Benign	0.64
PhyloP100		-0.76
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs9267673; hg19: chr6-31883679;