Variant 1-151837935-C-A 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.1055G>T(p.Ser352Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000548 in 1,533,404 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000049 ( 1 hom. )

Consequence

C2CD4D
NM_001394591.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.806

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=0.044051766).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
C2CD4D	NM_001394591.1 linkuse as main transcript	c.1055G>T	p.Ser352Ile	missense_variant	2/2	ENST00000694868.1	NP_001381520.1
C2CD4D	NM_001136003.2 linkuse as main transcript	c.1055G>T	p.Ser352Ile	missense_variant	2/2		NP_001129475.1
C2CD4D	NM_001394592.1 linkuse as main transcript	c.1055G>T	p.Ser352Ile	missense_variant	2/2		NP_001381521.1
C2CD4D	NM_001394593.1 linkuse as main transcript	c.1055G>T	p.Ser352Ile	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.1055G>T	p.Ser352Ile	missense_variant	2/2		NM_001394591.1	ENSP00000511551	P1
C2CD4D	ENST00000454109.1 linkuse as main transcript	c.1055G>T	p.Ser352Ile	missense_variant	2/2	2		ENSP00000389554	P1
C2CD4D	ENST00000694869.1 linkuse as main transcript	c.1055G>T	p.Ser352Ile	missense_variant	2/2			ENSP00000511552	P1

Frequencies

GnomAD3 genomes

AF:

0.000112

AC:

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000362

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.000478

GnomAD3 exomes

AF:

0.0000703

AC:

AN:

142280

Hom.:

AF XY:

0.0000532

AC XY:

AN XY:

75138

show subpopulations

Gnomad AFR exome

AF:

0.000391

Gnomad AMR exome

AF:

0.0000427

Gnomad ASJ exome

AF:

0.000137

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000489

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000369

Gnomad OTH exome

AF:

0.000497

GnomAD4 exome

AF:

0.0000485

AC:

AN:

1381072

Hom.:

Cov.:

AF XY:

0.0000413

AC XY:

AN XY:

678672

show subpopulations

Gnomad4 AFR exome

AF:

0.00128

Gnomad4 AMR exome

AF:

0.0000289

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000130

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000375

Gnomad4 OTH exome

AF:

0.000210

GnomAD4 genome

AF:

0.000112

AC:

AN:

152332

Hom.:

Cov.:

AF XY:

0.0000805

AC XY:

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.000361

Gnomad4 AMR

AF:

0.0000653

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:

0.000473

Alfa

AF:

0.000102

Hom.:

Bravo

AF:

0.000151

ESP6500AA

AF:

0.000723

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000129

AC:

Asia WGS

AF:

0.00173

AC:

AN:

3478

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

Feb 15, 2023

The c.1055G>T (p.S352I) alteration is located in exon 2 (coding exon 1) of the C2CD4D gene. This alteration results from a G to T substitution at nucleotide position 1055, causing the serine (S) at amino acid position 352 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

Benign

0.31

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0088

Eigen

Benign

-0.50

Eigen_PC

Benign

-0.39

FATHMM_MKL

Benign

0.63

LIST_S2

Benign

0.40

M_CAP

Benign

0.0086

MetaRNN

Benign

0.044

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.1

MutationTaster

Benign

0.98

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-1.1

REVEL

Benign

0.045

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.027

Vest4

0.20

MVP

0.25

ClinPred

0.080

GERP RS

1.9

Varity_R

0.25

gMVP

0.69

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