X-106927946-CAT-C

Position:

• chrX-106927946-CAT-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.37

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]

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]

ACMG classification

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	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLDN2	NM_020384.4	c.-178-104_-178-103del		intron_variant		ENST00000336803.2	NP_065117.1
CLDN2	NM_001171092.1	c.-178-104_-178-103del		intron_variant			NP_001164563.1
CLDN2	NM_001171095.2	c.-178-104_-178-103del		intron_variant			NP_001164566.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLDN2	ENST00000336803.2	c.-178-104_-178-103del		intron_variant		2	NM_020384.4	ENSP00000336571	P1
CLDN2	ENST00000540876.1	c.-178-104_-178-103del		intron_variant		1		ENSP00000443230	P1
CLDN2	ENST00000541806.6	c.-178-104_-178-103del		intron_variant		1		ENSP00000441283	P1
MORC4	ENST00000604604.1	c.111+65282_111+65283del		intron_variant		2		ENSP00000474750

Frequencies

GnomAD3 genomes AF: 0.165 AC: 18185 AN: 110421 Hom.: 1563 Cov.: 19 AF XY: 0.167 AC XY: 5486 AN XY: 32939

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

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.: 19 AF XY: 0.166 AC XY: 5482 AN XY: 32988

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

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2019

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs72466477; hg19: chrX-106171176;