Genetic Variant CLDND2:p.Ala143Ala (chr19-51367458-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2

The NM_152353.3(CLDND2):c.429G>A(p.Ala143Ala) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00316 in 1,597,596 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0018 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0033 ( 20 hom. )

Consequence

CLDND2
NM_152353.3 splice_region, synonymous

Scores

Splicing: ADA: 0.008737

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0260

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]

CLDND2 links:

ENSG00000269403 (HGNC:):

ENSG00000269403 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.32).

BP6

Variant 19-51367458-C-T is Benign according to our data. Variant chr19-51367458-C-T is described in ClinVar as [Benign]. Clinvar id is 2650373.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 20 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLDND2	NM_152353.3 link	c.429G>A	p.Ala143Ala	splice_region_variant, synonymous_variant	Exon 3 of 4	ENST00000291715.5	NP_689566.1	Q8NHS1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CLDND2	ENST00000291715.5 link	c.429G>A	p.Ala143Ala	splice_region_variant, synonymous_variant	Exon 3 of 4	1	NM_152353.3	ENSP00000291715.1	Q8NHS1
ENSG00000269403	ENST00000600067.1 link	n.115+428G>A		intron_variant	Intron 1 of 3	5		ENSP00000469452.1	M0QXX7
CLDND2	ENST00000601435.1 link	c.429G>A	p.Ala143Ala	splice_region_variant, synonymous_variant	Exon 4 of 5	3		ENSP00000472077.1	Q8NHS1
CLDND2	ENST00000593841.1 link	c.119-61G>A		intron_variant	Intron 2 of 2	5		ENSP00000471912.1	M0R1J6

Frequencies

GnomAD3 genomes

AF:

0.00179

AC:

272

AN:

152114

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000386

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000524

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00914

Gnomad FIN

AF:

0.000754

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00282

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.00282

AC:

634

AN:

224462

Hom.:

AF XY:

0.00336

AC XY:

406

AN XY:

120950

show subpopulations

Gnomad AFR exome

AF:

0.000503

Gnomad AMR exome

AF:

0.000571

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000596

Gnomad SAS exome

AF:

0.0107

Gnomad FIN exome

AF:

0.00148

Gnomad NFE exome

AF:

0.00270

Gnomad OTH exome

AF:

0.00160

GnomAD4 exome

AF:

0.00331

AC:

4782

AN:

1445364

Hom.:

Cov.:

AF XY:

0.00352

AC XY:

2524

AN XY:

717474

show subpopulations

Gnomad4 AFR exome

AF:

0.000511

Gnomad4 AMR exome

AF:

0.000809

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000509

Gnomad4 SAS exome

AF:

0.0103

Gnomad4 FIN exome

AF:

0.00172

Gnomad4 NFE exome

AF:

0.00324

Gnomad4 OTH exome

AF:

0.00261

GnomAD4 genome

AF:

0.00178

AC:

271

AN:

152232

Hom.:

Cov.:

AF XY:

0.00181

AC XY:

135

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.000385

Gnomad4 AMR

AF:

0.000523

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00914

Gnomad4 FIN

AF:

0.000754

Gnomad4 NFE

AF:

0.00282

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00263

Hom.:

Bravo

AF:

0.00156

Asia WGS

AF:

0.00260

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jul 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

CLDND2: PP3, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Benign

0.87

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0087

dbscSNV1_RF

Benign

0.094

SpliceAI score (max)

0.93

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.93

Position offset: -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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over