Variant 1-151838485-G-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_001394591.1(C2CD4D):c.505C>G(p.Leu169Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000572 in 1,397,384 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000040 ( 0 hom. )

Consequence

C2CD4D
NM_001394591.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.19

Variant links:

Genes affected

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

C2CD4D links:

C2CD4D-AS1 (HGNC:):

C2CD4D-AS1 links:

Genome browser will be placed here

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=0.11620122).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C2CD4D	NM_001394591.1 linkuse as main transcript	c.505C>G	p.Leu169Val	missense_variant	2/2	ENST00000694868.1	NP_001381520.1
C2CD4D-AS1	NR_024237.2 linkuse as main transcript	n.209G>C		non_coding_transcript_exon_variant	1/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
C2CD4D	ENST00000694868.1 linkuse as main transcript	c.505C>G	p.Leu169Val	missense_variant	2/2		NM_001394591.1	ENSP00000511551	P1
C2CD4D	ENST00000454109.1 linkuse as main transcript	c.505C>G	p.Leu169Val	missense_variant	2/2	2		ENSP00000389554	P1
C2CD4D	ENST00000694869.1 linkuse as main transcript	c.505C>G	p.Leu169Val	missense_variant	2/2			ENSP00000511552	P1

Frequencies

GnomAD3 genomes

AF:

0.0000198

AC:

AN:

151636

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000725

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

GnomAD4 exome

AF:

0.00000401

AC:

AN:

1245748

Hom.:

Cov.:

AF XY:

0.00000328

AC XY:

AN XY:

610350

show subpopulations

Gnomad4 AFR exome

AF:

0.000120

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:

9.88e-7

Gnomad4 OTH exome

AF:

0.0000196

GnomAD4 genome

AF:

0.0000198

AC:

AN:

151636

Hom.:

Cov.:

AF XY:

0.0000270

AC XY:

AN XY:

74062

show subpopulations

Gnomad4 AFR

AF:

0.0000725

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:

0.0000712

Hom.:

Bravo

AF:

0.0000378

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 26, 2022

The c.505C>G (p.L169V) alteration is located in exon 2 (coding exon 1) of the C2CD4D gene. This alteration results from a C to G substitution at nucleotide position 505, causing the leucine (L) at amino acid position 169 to be replaced by a valine (V). 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

0.071

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.65

CADD

Benign

DANN

Benign

0.87

DEOGEN2

Benign

0.027

Eigen

Benign

-0.51

Eigen_PC

Benign

-0.56

FATHMM_MKL

Benign

0.65

LIST_S2

Benign

0.41

M_CAP

Benign

0.016

MetaRNN

Benign

0.12

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

MutationTaster

Benign

0.99

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-1.1

REVEL

Benign

0.057

Sift

Benign

0.071

Sift4G

Benign

0.13

Polyphen

0.58

Vest4

0.097

MutPred

0.14

Loss of catalytic residue at L169 (P = 0.0898);

MVP

0.048

ClinPred

0.12

GERP RS

2.4

Varity_R

0.13

gMVP

0.20

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