rs10931959

Positions:

• chr2-201569730-A-C
• chr2-201569730-A-G
• chr2-201569730-A-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000439140.6(C2CD6):​c.833+2211T>G variant causes a intron 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: C2CD6 ENST00000439140.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.319

Genes affected

C2CD6 (HGNC:14438): (C2 calcium dependent domain containing 6) An autosomal recessive form of juvenile amyotrophic lateral sclerosis was originally mapped to a region of chromosome 2 that includes this gene. The encoded protein contains a calcium-dependent membrane targeting C2 domain. This domain is often found in proteins that are involved in membrane trafficking and signal transduction. [provided by RefSeq, Jun 2016]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C2CD6	NM_001168221.2	c.833+2211T>G		intron_variant		ENST00000439140.6	NP_001161693.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C2CD6	ENST00000439140.6	c.833+2211T>G		intron_variant		1	NM_001168221.2	ENSP00000409937	A2
C2CD6	ENST00000286195.7	c.833+2211T>G		intron_variant		1		ENSP00000286195	P2
C2CD6	ENST00000450242.1	c.833+2211T>G		intron_variant		1		ENSP00000399016	A2
C2CD6	ENST00000439802.5	c.833+2211T>G		intron_variant		2		ENSP00000400672

Frequencies

GnomAD3 genomes Cov.: 31

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

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	7.0
DANN	Benign	0.61

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

Publications

LitVar

Other links and lift over

dbSNP: rs10931959; hg19: chr2-202434453;