rs137890141

Variant names:

• chr19-51368519-A-T
• rs137890141
• NM_152353.3:c.59T>A

Your query was ambiguous. Multiple possible variants found:

• chr19-51368519-A-T
• chr19-51368519-A-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_152353.3(CLDND2):​c.59T>A​(p.Val20Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000044 in 1,614,014 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00027 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000021 (0 hom.)
• Consequence: CLDND2 NM_152353.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.255
• Publications: 0 publications found

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]

ENSG00000297420 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.084100276).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152353.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLDND2	NM_152353.3	MANE Select	c.59T>A	p.Val20Asp	missense	Exon 1 of 4	NP_689566.1	Q8NHS1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLDND2	ENST00000291715.5	TSL:1 MANE Select	c.59T>A	p.Val20Asp	missense	Exon 1 of 4	ENSP00000291715.1	Q8NHS1
	CLDND2	ENST00000601435.1	TSL:3	c.59T>A	p.Val20Asp	missense	Exon 2 of 5	ENSP00000472077.1	Q8NHS1
	ENSG00000297420	ENST00000747813.1		n.356+1269A>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000269 AC: 41 AN: 152154 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000989

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000797 AC: 20 AN: 250924 AF XY: 0.0000369

Gnomad AFR exome AF: 0.000925

Gnomad AMR exome AF: 0.000145

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000205 AC: 30 AN: 1461742 Hom.: 0 Cov.: 31 AF XY: 0.0000138 AC XY: 10 AN XY: 727202

African (AFR) AF: 0.000687 AC: 23 AN: 33472

American (AMR) AF: 0.000112 AC: 5 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53342

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111972

Other (OTH) AF: 0.0000331 AC: 2 AN: 60394

GnomAD4 genome AF: 0.000269 AC: 41 AN: 152272 Hom.: 0 Cov.: 32 AF XY: 0.000175 AC XY: 13 AN XY: 74464

African (AFR) AF: 0.000986 AC: 41 AN: 41566

American (AMR) AF: 0.00 AC: 0 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67994

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.0000283 Hom.: 0

Bravo AF: 0.000298

ESP6500AA AF: 0.00113 AC: 5

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000741 AC: 9

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.62
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.10
CADD	Benign	21
DANN	Benign	0.96
DEOGEN2	Uncertain	0.65	D
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.40
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.47	T
M_CAP	Uncertain	0.15	D
MetaRNN	Benign	0.084	T
MetaSVM	Benign	-0.38	T
MutationAssessor	Benign	1.5	L
PhyloP100		0.26
PrimateAI	Benign	0.39	T
PROVEAN	Pathogenic	-5.4	D
REVEL	Uncertain	0.45
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0090	D
Polyphen		0.85	P
Vest4		0.46
MVP		0.77
MPC		1.3
ClinPred		0.28	T
GERP RS		3.2
PromoterAI		-0.015	Neutral
Varity_R		0.80
gMVP		0.79
Mutation Taster		=94/6	polymorphism

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

Other links and lift over

dbSNP: rs137890141; hg19: chr19-51871773;