19-51368544-T-G

Variant names:

• chr19-51368544-T-G
• NM_152353.3:c.34A>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_152353.3(CLDND2):​c.34A>C​(p.Ile12Leu) 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. 16/21 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0750

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]

ACMG classification

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=0.085011125).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLDND2	NM_152353.3	c.34A>C	p.Ile12Leu	missense_variant	Exon 1 of 4	ENST00000291715.5	NP_689566.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLDND2	ENST00000291715.5	c.34A>C	p.Ile12Leu	missense_variant	Exon 1 of 4	1	NM_152353.3	ENSP00000291715.1
CLDND2	ENST00000601435.1	c.34A>C	p.Ile12Leu	missense_variant	Exon 2 of 5	3		ENSP00000472077.1

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

Submissions by phenotype

not specified Uncertain:1

Sep 26, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.34A>C (p.I12L) alteration is located in exon 1 (coding exon 1) of the CLDND2 gene. This alteration results from a A to C substitution at nucleotide position 34, causing the isoleucine (I) at amino acid position 12 to be replaced by a leucine (L). 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	0.090
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	10
DANN	Benign	0.72
DEOGEN2	Benign	0.12	T;T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.43	.;T
M_CAP	Benign	0.040	D
MetaRNN	Benign	0.085	T;T
MetaSVM	Benign	-0.64	T
MutationAssessor	Benign	-1.1	N;N
PrimateAI	Benign	0.35	T
PROVEAN	Benign	0.77	N;.
REVEL	Benign	0.17
Sift	Benign	1.0	T;.
Sift4G	Benign	1.0	T;T
Polyphen		0.0	B;B
Vest4		0.091
MutPred		0.50		Loss of glycosylation at S9 (P = 0.0941);Loss of glycosylation at S9 (P = 0.0941);
MVP		0.38
MPC		0.31
ClinPred		0.080	T
GERP RS		-0.88
Varity_R		0.046
gMVP		0.34

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr19-51871798;