rs59278883

Positions:

• chr2-201515105-T-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001168221.2(C2CD6):​c.1507-19136A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 151,042 control chromosomes in the GnomAD database, including 1,877 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 0.13 (1877 hom., cov: 30)
• Consequence: C2CD6 NM_001168221.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.489

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.261 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C2CD6	NM_001168221.2	c.1507-19136A>T		intron_variant		ENST00000439140.6	NP_001161693.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C2CD6	ENST00000439140.6	c.1507-19136A>T		intron_variant		1	NM_001168221.2	ENSP00000409937	A2
C2CD6	ENST00000286195.7	c.1507-19136A>T		intron_variant		1		ENSP00000286195	P2
C2CD6	ENST00000439802.5	c.1163-19136A>T		intron_variant		2		ENSP00000400672

Frequencies

GnomAD3 genomes AF: 0.132 AC: 19890 AN: 150930 Hom.: 1864 Cov.: 30

Gnomad AFR AF: 0.241

Gnomad AMI AF: 0.0526

Gnomad AMR AF: 0.0958

Gnomad ASJ AF: 0.111

Gnomad EAS AF: 0.273

Gnomad SAS AF: 0.215

Gnomad FIN AF: 0.0254

Gnomad MID AF: 0.141

Gnomad NFE AF: 0.0757

Gnomad OTH AF: 0.122

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

GnomAD4 genome AF: 0.132 AC: 19929 AN: 151042 Hom.: 1877 Cov.: 30 AF XY: 0.132 AC XY: 9757 AN XY: 73662

Gnomad4 AFR AF: 0.242

Gnomad4 AMR AF: 0.0956

Gnomad4 ASJ AF: 0.111

Gnomad4 EAS AF: 0.273

Gnomad4 SAS AF: 0.215

Gnomad4 FIN AF: 0.0254

Gnomad4 NFE AF: 0.0757

Gnomad4 OTH AF: 0.122

Alfa AF: 0.103 Hom.: 158

Bravo AF: 0.140

Asia WGS AF: 0.253 AC: 878 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	4.1
DANN	Benign	0.42

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: rs59278883; hg19: chr2-202379828;