NM_152353.3:c.16A>G

Variant summary

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

The NM_152353.3(CLDND2):​c.16A>G​(p.Ser6Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 32)

Consequence

CLDND2
NM_152353.3 missense

Scores

6
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0720
Variant links:
Genes affected
CLDND2 (HGNC:28511): (claudin domain containing 2) Predicted to be integral component of membrane. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

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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=0.17049405).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CLDND2NM_152353.3 linkc.16A>G p.Ser6Gly missense_variant Exon 1 of 4 ENST00000291715.5 NP_689566.1 Q8NHS1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CLDND2ENST00000291715.5 linkc.16A>G p.Ser6Gly missense_variant Exon 1 of 4 1 NM_152353.3 ENSP00000291715.1 Q8NHS1
CLDND2ENST00000601435.1 linkc.16A>G p.Ser6Gly missense_variant Exon 2 of 5 3 ENSP00000472077.1 Q8NHS1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jul 13, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.16A>G (p.S6G) alteration is located in exon 1 (coding exon 1) of the CLDND2 gene. This alteration results from a A to G substitution at nucleotide position 16, causing the serine (S) at amino acid position 6 to be replaced by a glycine (G). 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
0.10
BayesDel_addAF
Uncertain
0.016
T
BayesDel_noAF
Benign
-0.22
CADD
Benign
21
DANN
Uncertain
1.0
DEOGEN2
Benign
0.044
T;T
Eigen
Benign
-0.48
Eigen_PC
Benign
-0.48
FATHMM_MKL
Benign
0.26
N
LIST_S2
Benign
0.39
.;T
M_CAP
Uncertain
0.29
D
MetaRNN
Benign
0.17
T;T
MetaSVM
Uncertain
0.18
D
MutationAssessor
Benign
2.0
M;M
PrimateAI
Benign
0.41
T
PROVEAN
Benign
-2.1
N;.
REVEL
Uncertain
0.33
Sift
Benign
0.087
T;.
Sift4G
Uncertain
0.048
D;D
Polyphen
0.029
B;B
Vest4
0.13
MutPred
0.49
Loss of stability (P = 0.0205);Loss of stability (P = 0.0205);
MVP
0.74
MPC
0.81
ClinPred
0.36
T
GERP RS
0.77
Varity_R
0.083
gMVP
0.22

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-51871816; API