6-31921092-T-G

Variant names:

• chr6-31921092-T-G
• rs511294
• ENST00000862556.1:c.-100+930T>G

Variant summary

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

The NM_001178063.3(C2):​c.74-12518T>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 NM_001178063.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.472
• Publications: 15 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=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001178063.3. 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.74-12518T>G		intron	N/A	NP_001171534.1
	C2	NM_001282457.2		c.-63-12518T>G		intron	N/A	NP_001269386.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C2	ENST00000862556.1		c.-100+930T>G		intron	N/A	ENSP00000532615.1
	C2	ENST00000695637.1		c.-359-6863T>G		intron	N/A	ENSP00000512074.1
	C2	ENST00000497706.6	TSL:5	c.-63-12518T>G		intron	N/A	ENSP00000417482.2

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

African (AFR) AF: 0.107 AC: 4443 AN: 41514

American (AMR) AF: 0.0734 AC: 1122 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0354 AC: 123 AN: 3472

East Asian (EAS) AF: 0.00502 AC: 26 AN: 5178

South Asian (SAS) AF: 0.0193 AC: 93 AN: 4824

European-Finnish (FIN) AF: 0.0394 AC: 418 AN: 10620

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0661 AC: 4495 AN: 68004

Other (OTH) AF: 0.0796 AC: 168 AN: 2110

Alfa AF: 0.0633 Hom.: 1027

Bravo AF: 0.0774

Asia WGS AF: 0.0150 AC: 51 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.5
DANN	Benign	0.81
PhyloP100		-0.47
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: rs511294; hg19: chr6-31888869;