X-106927928-G-GT

Position:

• chrX-106927928-G-GT

Variant summary

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

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.223

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-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	HGVSp	Effect	#exon/exons	MANE	UniProt
CLDN2	NM_020384.4	c.-178-113dup		intron_variant		ENST00000336803.2
CLDN2	NM_001171092.1	c.-178-113dup		intron_variant
CLDN2	NM_001171095.2	c.-178-113dup		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLDN2	ENST00000336803.2	c.-178-113dup		intron_variant		2	NM_020384.4	P1
CLDN2	ENST00000540876.1	c.-178-113dup		intron_variant		1		P1
CLDN2	ENST00000541806.6	c.-178-113dup		intron_variant		1		P1
MORC4	ENST00000604604.1	c.111+65301_111+65302insA		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.575 AC: 61697 AN: 107368 Hom.: 14145 Cov.: 0 AF XY: 0.572 AC XY: 17339 AN XY: 30310

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

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.: 0 AF XY: 0.572 AC XY: 17363 AN XY: 30330

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

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: rs34087972; hg19: chrX-106171158;