rs375588532

Variant names:

• chr12-22457135-C-A
• NM_001286176.2:c.2713G>T

Your query was ambiguous. Multiple possible variants found:

• chr12-22457135-C-A
• chr12-22457135-C-G
• chr12-22457135-C-T

Variant summary

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

The NM_001286176.2(C2CD5):​c.2713G>T​(p.Val905Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000689 in 1,451,510 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict 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: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: C2CD5 NM_001286176.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.296

Genes affected

C2CD5 (HGNC:29062): (C2 calcium dependent domain containing 5) Enables calcium ion binding activity and calcium-dependent phospholipid binding activity. Involved in cellular response to insulin stimulus; intracellular protein transmembrane transport; and positive regulation of transport. Located in several cellular components, including centriolar satellite; cytoplasmic vesicle membrane; and ruffle membrane. [provided by Alliance of Genome Resources, Apr 2022]

C2CD5-AS1 (HGNC:55961): (C2CD5 antisense RNA 1)

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 (MetaRNN=0.013308257).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C2CD5	NM_001286176.2	c.2713G>T	p.Val905Leu	missense_variant	Exon 25 of 27	ENST00000446597.6	NP_001273105.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C2CD5	ENST00000446597.6	c.2713G>T	p.Val905Leu	missense_variant	Exon 25 of 27	1	NM_001286176.2	ENSP00000388756.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.89e-7 AC: 1 AN: 1451510 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 721822

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000235

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	0.066
DANN	Benign	0.75
DEOGEN2	Benign	0.012	T;.;.;.;.;.
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.048	N
LIST_S2	Benign	0.79	T;.;T;T;T;T
M_CAP	Benign	0.0098	T
MetaRNN	Benign	0.013	T;T;T;T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-2.1	N;.;.;.;.;.
PrimateAI	Benign	0.31	T
PROVEAN	Benign	0.70	N;N;N;N;N;N
REVEL	Benign	0.10
Sift	Benign	1.0	T;T;T;T;T;T
Sift4G	Benign	0.97	T;T;T;T;T;T
Polyphen		0.0	B;.;.;B;.;.
Vest4		0.11
MutPred		0.22		Gain of catalytic residue at G857 (P = 0.0067);.;.;.;.;.;
MVP		0.17
MPC		0.39
ClinPred		0.053	T
GERP RS		-8.5
Varity_R		0.020
gMVP		0.27

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-22610069;