Variant chrX-106927928-G-GT 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.-178-113dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.333 in 78,970 control chromosomes in the GnomAD database, including 2,891 homozygotes. There are 3,670 hemizygotes in GnomAD. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.57 ( 14142 hom., 17363 hem., cov: 0)

Exomes 𝑓: 0.33 ( 2891 hom. 3670 hem. )

Failed GnomAD Quality Control

Consequence

CLDN2
NM_020384.4 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.223

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-106927928-G-GT is Benign according to our data. Variant chrX-106927928-G-GT is described in ClinVar as [Benign]. Clinvar id is 1278815.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.718 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
CLDN2	NM_020384.4 linkuse as main transcript	c.-178-113dup	intron_variant	ENST00000336803.2
CLDN2	NM_001171092.1 linkuse as main transcript	c.-178-113dup	intron_variant
CLDN2	NM_001171095.2 linkuse as main transcript	c.-178-113dup	intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris
CLDN2	ENST00000336803.2 linkuse as main transcript	c.-178-113dup	intron_variant	2	NM_020384.4	P1
CLDN2	ENST00000540876.1 linkuse as main transcript	c.-178-113dup	intron_variant	1		P1
CLDN2	ENST00000541806.6 linkuse as main transcript	c.-178-113dup	intron_variant	1		P1
MORC4	ENST00000604604.1 linkuse as main transcript	c.111+65301_111+65302insA	intron_variant	2

Frequencies

GnomAD3 genomes

AF:

0.575

AC:

61697

AN:

107368

Hom.:

14145

Cov.:

AF XY:

0.572

AC XY:

17339

AN XY:

30310

show subpopulations

Gnomad AFR

AF:

0.812

Gnomad AMI

AF:

0.219

Gnomad AMR

AF:

0.665

Gnomad ASJ

AF:

0.466

Gnomad EAS

AF:

0.917

Gnomad SAS

AF:

0.709

Gnomad FIN

AF:

0.375

Gnomad MID

AF:

0.372

Gnomad NFE

AF:

0.424

Gnomad OTH

AF:

0.562

GnomAD4 exome

AF:

0.333

AC:

26271

AN:

78970

Hom.:

2891

AF XY:

0.234

AC XY:

3670

AN XY:

15676

show subpopulations

Gnomad4 AFR exome

AF:

0.597

Gnomad4 AMR exome

AF:

0.522

Gnomad4 ASJ exome

AF:

0.306

Gnomad4 EAS exome

AF:

0.739

Gnomad4 SAS exome

AF:

0.484

Gnomad4 FIN exome

AF:

0.244

Gnomad4 NFE exome

AF:

0.289

Gnomad4 OTH exome

AF:

0.347

GnomAD4 genome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.575

AC:

61715

AN:

107376

Hom.:

14142

Cov.:

AF XY:

0.572

AC XY:

17363

AN XY:

30330

show subpopulations

Gnomad4 AFR

AF:

0.813

Gnomad4 AMR

AF:

0.665

Gnomad4 ASJ

AF:

0.466

Gnomad4 EAS

AF:

0.917

Gnomad4 SAS

AF:

0.707

Gnomad4 FIN

AF:

0.375

Gnomad4 NFE

AF:

0.424

Gnomad4 OTH

AF:

0.565

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