6-31922381-T-G

Variant names:

• chr6-31922381-T-G
• rs544167
• ENST00000695637.1:c.-359-5574T>G

Variant summary

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

The ENST00000695637.1(C2):​c.-359-5574T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0715 in 152,146 control chromosomes in the GnomAD database, including 413 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 (413 hom., cov: 32)
• Consequence: C2 ENST00000695637.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0340
• Publications: 20 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=-0.78).
• 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: 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.74-11229T>G		intron	N/A	NP_001171534.1
	C2	NM_001282457.2		c.-63-11229T>G		intron	N/A	NP_001269386.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C2	ENST00000695637.1		c.-359-5574T>G		intron	N/A	ENSP00000512074.1
	C2	ENST00000497706.6	TSL:5	c.-63-11229T>G		intron	N/A	ENSP00000417482.2
	C2	ENST00000452323.7	TSL:2	c.74-11229T>G		intron	N/A	ENSP00000392322.2

Frequencies

GnomAD3 genomes AF: 0.0715 AC: 10869 AN: 152028 Hom.: 412 Cov.: 32

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.0319

Gnomad AMR AF: 0.0730

Gnomad ASJ AF: 0.0354

Gnomad EAS AF: 0.00500

Gnomad SAS AF: 0.0195

Gnomad FIN AF: 0.0391

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0660

Gnomad OTH AF: 0.0810

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

GnomAD4 genome AF: 0.0715 AC: 10882 AN: 152146 Hom.: 413 Cov.: 32 AF XY: 0.0686 AC XY: 5104 AN XY: 74370

African (AFR) AF: 0.106 AC: 4411 AN: 41496

American (AMR) AF: 0.0729 AC: 1114 AN: 15272

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

East Asian (EAS) AF: 0.00501 AC: 26 AN: 5186

South Asian (SAS) AF: 0.0191 AC: 92 AN: 4816

European-Finnish (FIN) AF: 0.0391 AC: 415 AN: 10610

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

European-Non Finnish (NFE) AF: 0.0660 AC: 4487 AN: 67984

Other (OTH) AF: 0.0802 AC: 169 AN: 2108

Alfa AF: 0.0612 Hom.: 770

Bravo AF: 0.0772

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	-0.78
CADD	Benign	7.0
DANN	Benign	0.84
PhyloP100		-0.034
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: rs544167; hg19: chr6-31890158;