rs762993037

Variant summary

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

The NM_015500.2(C2CD2):​c.1987C>T​(p.Arg663Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,461,580 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict 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: 0.0000062 ( 0 hom. )

Consequence

C2CD2
NM_015500.2 missense

Scores

1
3
14

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.87
Variant links:
Genes affected
C2CD2 (HGNC:1266): (C2 calcium dependent domain containing 2) Located in cytosol and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

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=0.2427223).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
C2CD2NM_015500.2 linkc.1987C>T p.Arg663Trp missense_variant Exon 14 of 14 ENST00000380486.4 NP_056315.1 Q9Y426-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
C2CD2ENST00000380486.4 linkc.1987C>T p.Arg663Trp missense_variant Exon 14 of 14 1 NM_015500.2 ENSP00000369853.3 Q9Y426-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000796
AC:
2
AN:
251316
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135896
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000289
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000616
AC:
9
AN:
1461580
Hom.:
0
Cov.:
32
AF XY:
0.00000825
AC XY:
6
AN XY:
727096
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000540
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.0000151
ExAC
AF:
0.0000165
AC:
2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.13
BayesDel_addAF
Benign
-0.045
T
BayesDel_noAF
Benign
-0.21
CADD
Uncertain
26
DANN
Uncertain
1.0
DEOGEN2
Benign
0.34
.;T
Eigen
Benign
-0.11
Eigen_PC
Benign
-0.22
FATHMM_MKL
Benign
0.18
N
LIST_S2
Benign
0.82
T;T
M_CAP
Benign
0.037
D
MetaRNN
Benign
0.24
T;T
MetaSVM
Benign
-0.86
T
PrimateAI
Benign
0.30
T
PROVEAN
Pathogenic
-5.8
D;D
REVEL
Benign
0.20
Sift
Uncertain
0.0010
D;D
Sift4G
Uncertain
0.0020
D;D
Polyphen
1.0
.;D
Vest4
0.29
MutPred
0.46
.;Loss of disorder (P = 8e-04);
MVP
0.75
MPC
0.85
ClinPred
0.90
D
GERP RS
3.3
Varity_R
0.21
gMVP
0.18

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.

Other links and lift over

dbSNP: rs762993037; hg19: chr21-43309337; API