19-51368417-G-T

Variant names:

• chr19-51368417-G-T
• NM_152353.3:c.161C>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_152353.3(CLDND2):​c.161C>A​(p.Pro54His) 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.995

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31659454).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLDND2	NM_152353.3	c.161C>A	p.Pro54His	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.161C>A	p.Pro54His	missense_variant	Exon 1 of 4	1	NM_152353.3	ENSP00000291715.1
CLDND2	ENST00000601435.1	c.161C>A	p.Pro54His	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

Feb 10, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.161C>A (p.P54H) alteration is located in exon 1 (coding exon 1) of the CLDND2 gene. This alteration results from a C to A substitution at nucleotide position 161, causing the proline (P) at amino acid position 54 to be replaced by a histidine (H). 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	0.16
BayesDel_addAF	Benign	-0.025	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.29	T;T
Eigen	Benign	-0.028
Eigen_PC	Benign	-0.15
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.39	.;T
M_CAP	Uncertain	0.15	D
MetaRNN	Benign	0.32	T;T
MetaSVM	Uncertain	-0.15	T
MutationAssessor	Uncertain	2.0	M;M
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.68	N;.
REVEL	Uncertain	0.30
Sift	Benign	0.098	T;.
Sift4G	Uncertain	0.0060	D;D
Polyphen		0.99	D;D
Vest4		0.30
MutPred		0.49		Loss of helix (P = 0.0626);Loss of helix (P = 0.0626);
MVP		0.85
MPC		1.1
ClinPred		0.67	D
GERP RS		0.74
Varity_R		0.081
gMVP		0.32

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: chr19-51871671;