chr15-62164258-C-T

Variant summary

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

The NM_001007595.3(C2CD4B):​c.727G>A​(p.Val243Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000208 in 1,441,834 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 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 7.8e-7 ( 0 hom. )

Consequence

C2CD4B
NM_001007595.3 missense

Scores

1
5
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0490
Variant links:
Genes affected
C2CD4B (HGNC:33628): (C2 calcium dependent domain containing 4B) Involved in positive regulation of acute inflammatory response; regulation of cell adhesion; and regulation of vascular permeability involved in acute inflammatory response. [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=0.17263848).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
C2CD4BNM_001007595.3 linkc.727G>A p.Val243Met missense_variant Exon 2 of 2 ENST00000380392.4 NP_001007596.2 A6NLJ0

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
C2CD4BENST00000380392.4 linkc.727G>A p.Val243Met missense_variant Exon 2 of 2 2 NM_001007595.3 ENSP00000369755.3 A6NLJ0

Frequencies

GnomAD3 genomes
AF:
0.0000132
AC:
2
AN:
151972
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
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:
7.75e-7
AC:
1
AN:
1289862
Hom.:
0
Cov.:
37
AF XY:
0.00000157
AC XY:
1
AN XY:
635194
show subpopulations
Gnomad4 AFR exome
AF:
0.00
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:
9.63e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000132
AC:
2
AN:
151972
Hom.:
0
Cov.:
33
AF XY:
0.0000269
AC XY:
2
AN XY:
74224
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000131
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
Bravo
AF:
0.0000264

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jun 29, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.727G>A (p.V243M) alteration is located in exon 2 (coding exon 1) of the C2CD4B gene. This alteration results from a G to A substitution at nucleotide position 727, causing the valine (V) at amino acid position 243 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
Uncertain
0.36
BayesDel_addAF
Benign
-0.22
T
BayesDel_noAF
Benign
-0.55
CADD
Benign
18
DANN
Benign
0.95
DEOGEN2
Benign
0.11
T
Eigen
Benign
-0.80
Eigen_PC
Benign
-0.97
FATHMM_MKL
Benign
0.21
N
LIST_S2
Benign
0.60
T
M_CAP
Uncertain
0.12
D
MetaRNN
Benign
0.17
T
MetaSVM
Benign
-0.84
T
MutationAssessor
Uncertain
2.9
M
PrimateAI
Pathogenic
0.92
D
PROVEAN
Benign
-2.1
N
REVEL
Benign
0.15
Sift
Uncertain
0.0040
D
Sift4G
Uncertain
0.0080
D
Polyphen
0.97
D
Vest4
0.036
MutPred
0.24
Loss of sheet (P = 0.0104);
MVP
0.37
MPC
0.93
ClinPred
0.61
D
GERP RS
0.77
Varity_R
0.14
gMVP
0.082

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: rs1157696339; hg19: chr15-62456457; API