15-62067953-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_207322.3(C2CD4A):​c.340A>T​(p.Thr114Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000216 in 1,391,060 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000022 ( 0 hom. )

Consequence

C2CD4A
NM_207322.3 missense

Scores

3
14
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.98
Variant links:
Genes affected
C2CD4A (HGNC:33627): (C2 calcium dependent domain containing 4A) Involved in positive regulation of acute inflammatory response; regulation of cell adhesion; and regulation of vascular permeability involved in acute inflammatory response. Located in 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 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
C2CD4ANM_207322.3 linkc.340A>T p.Thr114Ser missense_variant Exon 2 of 2 ENST00000355522.5 NP_997205.2 Q8NCU7

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
C2CD4AENST00000355522.5 linkc.340A>T p.Thr114Ser missense_variant Exon 2 of 2 1 NM_207322.3 ENSP00000347712.5 Q8NCU7

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000725
AC:
1
AN:
137974
Hom.:
0
AF XY:
0.0000130
AC XY:
1
AN XY:
76722
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000443
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000216
AC:
3
AN:
1391060
Hom.:
0
Cov.:
31
AF XY:
0.00000291
AC XY:
2
AN XY:
687980
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000280
Gnomad4 SAS exome
AF:
0.0000251
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.00000964
AC:
1

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Sep 27, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.340A>T (p.T114S) alteration is located in exon 2 (coding exon 1) of the C2CD4A gene. This alteration results from a A to T substitution at nucleotide position 340, causing the threonine (T) at amino acid position 114 to be replaced by a serine (S). 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
0.53
BayesDel_addAF
Uncertain
0.046
T
BayesDel_noAF
Uncertain
-0.040
CADD
Uncertain
25
DANN
Uncertain
0.99
DEOGEN2
Benign
0.37
T
Eigen
Uncertain
0.63
Eigen_PC
Uncertain
0.54
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Uncertain
0.88
D
M_CAP
Pathogenic
0.34
D
MetaRNN
Uncertain
0.43
T
MetaSVM
Uncertain
-0.011
T
MutationAssessor
Pathogenic
3.3
M
PrimateAI
Pathogenic
0.89
D
PROVEAN
Uncertain
-3.5
D
REVEL
Uncertain
0.31
Sift
Uncertain
0.021
D
Sift4G
Uncertain
0.018
D
Polyphen
1.0
D
Vest4
0.36
MutPred
0.28
Gain of relative solvent accessibility (P = 0.0166);
MVP
0.87
ClinPred
0.98
D
GERP RS
4.0
Varity_R
0.32
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: rs776405638; hg19: chr15-62360152; API