Variant chr12-22474812-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PM2

The NM_001286176.2(C2CD5):c.1982G>T(p.Ser661Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000048 in 1,458,222 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

C2CD5
NM_001286176.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.16

Variant links:

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 links:

C2CD5 (HGNC:):

C2CD5 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM1

In a modified_residue Phosphoserine (size 0) in uniprot entity C2CD5_HUMAN

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C2CD5	NM_001286176.2 linkuse as main transcript	c.1982G>T	p.Ser661Ile	missense_variant	16/27	ENST00000446597.6	NP_001273105.1	Q86YS7-3B7ZLK1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C2CD5	ENST00000446597.6 linkuse as main transcript	c.1982G>T	p.Ser661Ile	missense_variant	16/27	1	NM_001286176.2	ENSP00000388756.1		Q86YS7-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000480

AC:

AN:

1458222

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725354

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.00000541

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 25, 2024

The c.1982G>T (p.S661I) alteration is located in exon 16 (coding exon 15) of the C2CD5 gene. This alteration results from a G to T substitution at nucleotide position 1982, causing the serine (S) at amino acid position 661 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.58

BayesDel_addAF

Pathogenic

0.29

BayesDel_noAF

Pathogenic

0.17

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.34

T;.;.;.;.;.

Eigen

Pathogenic

0.77

Eigen_PC

Pathogenic

0.75

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.95

D;.;D;D;D;D

M_CAP

Benign

0.057

MetaRNN

Uncertain

0.53

D;D;D;D;D;D

MetaSVM

Benign

-0.40

MutationAssessor

Uncertain

2.3

M;M;.;.;M;.

PrimateAI

Uncertain

0.72

PROVEAN

Uncertain

-3.5

D;D;D;D;D;D

REVEL

Uncertain

0.34

Sift

Uncertain

0.0020

D;D;D;D;D;D

Sift4G

Uncertain

0.014

D;D;D;D;D;D

Polyphen

0.99

D;.;.;D;.;.

Vest4

0.67

MutPred

0.13

Loss of phosphorylation at S661 (P = 0.0062);Loss of phosphorylation at S661 (P = 0.0062);.;.;Loss of phosphorylation at S661 (P = 0.0062);.;

MVP

0.76

MPC

1.1

ClinPred

0.99

GERP RS

5.2

Varity_R

0.66

gMVP

0.70

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over