Variant chr12-22469744-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001286176.2(C2CD5):c.2498A>G(p.Asp833Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000275 in 1,454,192 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 32)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

C2CD5
NM_001286176.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.98

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.21350232).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C2CD5	NM_001286176.2 linkuse as main transcript	c.2498A>G	p.Asp833Gly	missense_variant	22/27	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.2498A>G	p.Asp833Gly	missense_variant	22/27	1	NM_001286176.2	ENSP00000388756.1		Q86YS7-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000818

AC:

AN:

244446

Hom.:

AF XY:

0.00000755

AC XY:

AN XY:

132444

show subpopulations

Gnomad AFR exome

AF:

0.0000639

Gnomad AMR exome

AF:

0.0000301

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000275

AC:

AN:

1454192

Hom.:

Cov.:

AF XY:

0.00000415

AC XY:

AN XY:

723398

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000456

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:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000151

ExAC

AF:

0.00000824

AC:

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

Oct 29, 2024

The c.2498A>G (p.D833G) alteration is located in exon 22 (coding exon 21) of the C2CD5 gene. This alteration results from a A to G substitution at nucleotide position 2498, causing the aspartic acid (D) at amino acid position 833 to be replaced by a glycine (G). 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

Benign

0.23

BayesDel_addAF

Benign

-0.093

BayesDel_noAF

Benign

-0.19

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.063

T;.;.;.;.;.

Eigen

Uncertain

0.26

Eigen_PC

Uncertain

0.34

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.94

D;.;D;D;D;D

M_CAP

Benign

0.023

MetaRNN

Benign

0.21

T;T;T;T;T;T

MetaSVM

Benign

-0.82

MutationAssessor

Uncertain

2.2

M;M;.;.;M;.

PrimateAI

Uncertain

0.61

PROVEAN

Uncertain

-2.4

N;N;N;N;N;N

REVEL

Benign

0.15

Sift

Benign

0.14

T;T;T;T;T;T

Sift4G

Benign

0.20

T;T;T;T;T;T

Polyphen

0.46

P;.;.;D;.;.

Vest4

0.31

MutPred

0.21

Gain of catalytic residue at L830 (P = 0.0061);Gain of catalytic residue at L830 (P = 0.0061);.;.;Gain of catalytic residue at L830 (P = 0.0061);.;

MVP

0.72

MPC

0.57

ClinPred

0.33

GERP RS

4.9

Varity_R

0.22

gMVP

0.44

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.20

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.20

Position offset: 1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over