15-62164003-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.982G>A​(p.Glu328Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000276 in 1,449,140 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 34)
Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

C2CD4B
NM_001007595.3 missense

Scores

5
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.678
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=0.24775937).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
C2CD4BNM_001007595.3 linkc.982G>A p.Glu328Lys 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.982G>A p.Glu328Lys missense_variant Exon 2 of 2 2 NM_001007595.3 ENSP00000369755.3 A6NLJ0

Frequencies

GnomAD3 genomes
Cov.:
34
GnomAD4 exome
AF:
0.00000276
AC:
4
AN:
1449140
Hom.:
0
Cov.:
29
AF XY:
0.00000278
AC XY:
2
AN XY:
720132
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:
0.00000361
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
34
Bravo
AF:
0.00000378

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jul 12, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.982G>A (p.E328K) 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 982, causing the glutamic acid (E) at amino acid position 328 to be replaced by a lysine (K). 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
0.22
BayesDel_addAF
Benign
-0.040
T
BayesDel_noAF
Benign
-0.30
CADD
Benign
21
DANN
Uncertain
1.0
DEOGEN2
Benign
0.032
T
Eigen
Benign
-0.18
Eigen_PC
Benign
-0.22
FATHMM_MKL
Benign
0.69
D
LIST_S2
Benign
0.71
T
M_CAP
Uncertain
0.11
D
MetaRNN
Benign
0.25
T
MetaSVM
Benign
-0.45
T
MutationAssessor
Benign
1.4
L
PrimateAI
Uncertain
0.65
T
PROVEAN
Benign
-1.9
N
REVEL
Uncertain
0.29
Sift
Benign
0.040
D
Sift4G
Uncertain
0.042
D
Polyphen
0.78
P
Vest4
0.18
MutPred
0.48
Gain of MoRF binding (P = 0.0075);
MVP
0.85
MPC
0.97
ClinPred
0.90
D
GERP RS
1.4
Varity_R
0.087
gMVP
0.32

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs1215508124; hg19: chr15-62456202; API