rs776263411

Variant names:

• chr6-31927716-C-A
• rs776263411
• ENST00000456570.5:c.-37C>A

Your query was ambiguous. Multiple possible variants found:

• chr6-31927716-C-A
• chr6-31927716-C-G
• chr6-31927716-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000418949.6(C2):​c.-37C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: C2 ENST00000418949.6 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:2
• Conservation: PhyloP100: -1.17
• Publications: 0 publications found

Genes affected

ENSG00000244255 (HGNC:):

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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000418949.6. 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_001178063.3		c.74-5894C>A		intron	N/A	NP_001171534.1	P06681-2
	C2	NM_001282457.2		c.-63-5894C>A		intron	N/A	NP_001269386.1	B4DQI1
	C2	NM_000063.6	MANE Select	c.-37C>A		upstream_gene	N/A	NP_000054.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000244255	ENST00000456570.5	TSL:2	c.-37C>A		5_prime_UTR	Exon 1 of 30	ENSP00000410815.1	B4E1Z4
	C2	ENST00000418949.6	TSL:1	c.-37C>A		5_prime_UTR	Exon 1 of 6	ENSP00000406190.2	Q8N6L6
	C2	ENST00000447952.7	TSL:3	c.-37C>A		5_prime_UTR	Exon 1 of 17	ENSP00000391354.3	F2Z3N2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Age related macular degeneration 14 (1)
-	1	-	Complement component 2 deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.65
DANN	Benign	0.68
PhyloP100		-1.2
PromoterAI		-0.28	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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

Other links and lift over

dbSNP: rs776263411; hg19: chr6-31895493;