19-51367458-C-T

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

2
Splicing: ADA: 0.008737
2

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]

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
CLDND2NM_152353.3 linkc.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 Appris UniProt
CLDND2ENST00000291715.5 linkc.429G>A p.Ala143Ala splice_region_variant, synonymous_variant Exon 3 of 4 1 NM_152353.3 ENSP00000291715.1 Q8NHS1
ENSG00000269403ENST00000600067.1 linkn.115+428G>A intron_variant Intron 1 of 3 5 ENSP00000469452.1 M0QXX7
CLDND2ENST00000601435.1 linkc.429G>A p.Ala143Ala splice_region_variant, synonymous_variant Exon 4 of 5 3 ENSP00000472077.1 Q8NHS1
CLDND2ENST00000593841.1 linkc.119-61G>A intron_variant Intron 2 of 2 5 ENSP00000471912.1 M0R1J6

Frequencies

GnomAD3 genomes
AF:
0.00179
AC:
272
AN:
152114
Hom.:
1
Cov.:
32
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.:
5
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.:
20
Cov.:
31
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.:
1
Cov.:
32
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.:
1
Bravo
AF:
0.00156
Asia WGS
AF:
0.00260
AC:
9
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
22
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.

Other links and lift over

dbSNP: rs143501994; hg19: chr19-51870712; COSMIC: COSV105837971; COSMIC: COSV105837971; API