Variant 1-151838161-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001394591.1(C2CD4D):c.829G>A(p.Val277Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000393 in 1,550,996 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00024 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

C2CD4D
NM_001394591.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.450

Variant links:

Genes affected

C2CD4D (HGNC:37210): (C2 calcium dependent domain containing 4D)

C2CD4D links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.05391687).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
C2CD4D	NM_001394591.1 linkuse as main transcript	c.829G>A	p.Val277Met	missense_variant	2/2	ENST00000694868.1	NP_001381520.1
C2CD4D	NM_001136003.2 linkuse as main transcript	c.829G>A	p.Val277Met	missense_variant	2/2		NP_001129475.1
C2CD4D	NM_001394592.1 linkuse as main transcript	c.829G>A	p.Val277Met	missense_variant	2/2		NP_001381521.1
C2CD4D	NM_001394593.1 linkuse as main transcript	c.829G>A	p.Val277Met	missense_variant	2/2		NP_001381522.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
C2CD4D	ENST00000694868.1 linkuse as main transcript	c.829G>A	p.Val277Met	missense_variant	2/2		NM_001394591.1	ENSP00000511551	P1
C2CD4D	ENST00000454109.1 linkuse as main transcript	c.829G>A	p.Val277Met	missense_variant	2/2	2		ENSP00000389554	P1
C2CD4D	ENST00000694869.1 linkuse as main transcript	c.829G>A	p.Val277Met	missense_variant	2/2			ENSP00000511552	P1

Frequencies

GnomAD3 genomes

AF:

0.000250

AC:

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000917

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000332

AC:

AN:

150690

Hom.:

AF XY:

0.0000249

AC XY:

AN XY:

80462

show subpopulations

Gnomad AFR exome

AF:

0.000513

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000922

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:

0.0000172

AC:

AN:

1398726

Hom.:

Cov.:

AF XY:

0.0000174

AC XY:

AN XY:

689904

show subpopulations

Gnomad4 AFR exome

AF:

0.000697

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:

0.00

Gnomad4 OTH exome

AF:

0.0000345

GnomAD4 genome

AF:

0.000243

AC:

AN:

152270

Hom.:

Cov.:

AF XY:

0.000228

AC XY:

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.000890

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000388

Hom.:

Bravo

AF:

0.000302

ExAC

AF:

0.000140

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

Apr 11, 2023

The c.829G>A (p.V277M) alteration is located in exon 2 (coding exon 1) of the C2CD4D gene. This alteration results from a G to A substitution at nucleotide position 829, causing the valine (V) at amino acid position 277 to be replaced by a methionine (M). 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

0.32

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.36

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.29

Eigen

Uncertain

0.32

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Benign

0.56

LIST_S2

Benign

0.58

M_CAP

Uncertain

0.22

MetaRNN

Benign

0.054

MetaSVM

Benign

-0.72

MutationAssessor

Uncertain

2.2

MutationTaster

Benign

0.95

PrimateAI

Pathogenic

0.90

PROVEAN

Benign

-2.1

REVEL

Uncertain

0.40

Sift

Uncertain

0.0050

Sift4G

Uncertain

0.0070

Polyphen

0.99

Vest4

0.22

MVP

0.43

ClinPred

0.23

GERP RS

2.3

Varity_R

0.22

gMVP

0.29

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

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