Variant X-106927946-CAT-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_020384.4(CLDN2):c.-178-104_-178-103del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 241,541 control chromosomes in the GnomAD database, including 4,671 homozygotes. There are 11,842 hemizygotes in GnomAD. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.16 ( 1563 hom., 5482 hem., cov: 19)

Exomes 𝑓: 0.21 ( 3108 hom. 6360 hem. )

Consequence

CLDN2
NM_020384.4 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.37

Variant links:

Genes affected

CLDN2 (HGNC:2041): (claudin 2) This gene product belongs to the claudin protein family whose members have been identified as major integral membrane proteins localized exclusively at tight junctions. Claudins are expressed in an organ-specific manner and regulate tissue-specific physiologic properties of tight junctions. This protein is expressed in the intestine. Alternatively spliced transcript variants with different 5' untranslated region have been found for this gene.[provided by RefSeq, Jan 2010]

CLDN2 links:

MORC4 (HGNC:23485): (MORC family CW-type zinc finger 4) In human, the four current members of the microrchidia (morc) gene family share an N-terminal ATPase-like ATP-binding region and a CW four-cysteine zinc-finger motif. The protein encoded by this gene also has a nuclear matrix binding domain and a two-stranded coiled-coil motif near its C-terminus. This gene is widely expressed at low levels in normal tissues and has elevated expression in placenta and testis. Alternative splicing results in multiple transcript variants encoding distinct proteins. [provided by RefSeq, Jan 2010]

MORC4 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant X-106927946-CAT-C is Benign according to our data. Variant chrX-106927946-CAT-C is described in ClinVar as [Benign]. Clinvar id is 1246131.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.504 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
CLDN2	NM_020384.4 linkuse as main transcript	c.-178-104_-178-103del	intron_variant	ENST00000336803.2
CLDN2	NM_001171092.1 linkuse as main transcript	c.-178-104_-178-103del	intron_variant
CLDN2	NM_001171095.2 linkuse as main transcript	c.-178-104_-178-103del	intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris
CLDN2	ENST00000336803.2 linkuse as main transcript	c.-178-104_-178-103del	intron_variant	2	NM_020384.4	P1
CLDN2	ENST00000540876.1 linkuse as main transcript	c.-178-104_-178-103del	intron_variant	1		P1
CLDN2	ENST00000541806.6 linkuse as main transcript	c.-178-104_-178-103del	intron_variant	1		P1
MORC4	ENST00000604604.1 linkuse as main transcript	c.111+65282_111+65283del	intron_variant	2

Frequencies

GnomAD3 genomes

AF:

0.165

AC:

18185

AN:

110421

Hom.:

1563

Cov.:

AF XY:

0.167

AC XY:

5486

AN XY:

32939

show subpopulations

Gnomad AFR

AF:

0.0554

Gnomad AMI

AF:

0.0893

Gnomad AMR

AF:

0.379

Gnomad ASJ

AF:

0.274

Gnomad EAS

AF:

0.525

Gnomad SAS

AF:

0.181

Gnomad FIN

AF:

0.127

Gnomad MID

AF:

0.189

Gnomad NFE

AF:

0.159

Gnomad OTH

AF:

0.208

GnomAD4 exome

AF:

0.205

AC:

26883

AN:

131075

Hom.:

3108

AF XY:

0.202

AC XY:

6360

AN XY:

31449

show subpopulations

Gnomad4 AFR exome

AF:

0.0586

Gnomad4 AMR exome

AF:

0.441

Gnomad4 ASJ exome

AF:

0.276

Gnomad4 EAS exome

AF:

0.566

Gnomad4 SAS exome

AF:

0.181

Gnomad4 FIN exome

AF:

0.140

Gnomad4 NFE exome

AF:

0.153

Gnomad4 OTH exome

AF:

0.199

GnomAD4 genome

AF:

0.164

AC:

18168

AN:

110466

Hom.:

1563

Cov.:

AF XY:

0.166

AC XY:

5482

AN XY:

32988

show subpopulations

Gnomad4 AFR

AF:

0.0553

Gnomad4 AMR

AF:

0.379

Gnomad4 ASJ

AF:

0.274

Gnomad4 EAS

AF:

0.524

Gnomad4 SAS

AF:

0.180

Gnomad4 FIN

AF:

0.127

Gnomad4 NFE

AF:

0.159

Gnomad4 OTH

AF:

0.204

Alfa

AF:

0.157

Hom.:

826

Asia WGS

AF:

0.303

AC:

762

AN:

2520

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

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