chrX-106927928-GT-G

Variant names:

• chrX-106927928-GT-G
• rs34087972
• NM_020384.4:c.-178-113delT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_020384.4(CLDN2):​c.-178-113delT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000172 in 192,366 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. There is a variant allele frequency bias in the population database for this variant (GnomAdExome4), which may indicate mosaicism or somatic mutations in the reference population data. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000028 (0 hom., 0 hem., cov: 0)
  • Exomes 𝑓: 0.00035 (0 hom. 0 hem.)
• Consequence: CLDN2 NM_020384.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.223
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020384.4. 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
	CLDN2	NM_020384.4	MANE Select	c.-178-113delT		intron	N/A	NP_065117.1	P57739
	CLDN2	NM_001171092.1		c.-178-113delT		intron	N/A	NP_001164563.1	P57739
	CLDN2	NM_001171095.2		c.-178-113delT		intron	N/A	NP_001164566.1	P57739

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLDN2	ENST00000336803.2	TSL:2 MANE Select	c.-178-122delT		intron	N/A	ENSP00000336571.1	P57739
	CLDN2	ENST00000540876.1	TSL:1	c.-178-122delT		intron	N/A	ENSP00000443230.1	P57739
	CLDN2	ENST00000541806.6	TSL:1	c.-178-122delT		intron	N/A	ENSP00000441283.1	P57739

Frequencies

GnomAD3 genomes AF: 0.0000279 AC: 3 AN: 107512 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

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: 0.0000386

Gnomad OTH AF: 0.000695

GnomAD4 exome AF: 0.000354 AC: 30 AN: 84845 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 20361

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000928 AC: 2 AN: 2156

American (AMR) AF: 0.00 AC: 0 AN: 2909

Ashkenazi Jewish (ASJ) AF: 0.000332 AC: 1 AN: 3011

East Asian (EAS) AF: 0.000207 AC: 1 AN: 4835

South Asian (SAS) AF: 0.00 AC: 0 AN: 1082

European-Finnish (FIN) AF: 0.000166 AC: 1 AN: 6018

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 409

European-Non Finnish (NFE) AF: 0.000427 AC: 25 AN: 58598

Other (OTH) AF: 0.00 AC: 0 AN: 5827

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000279 AC: 3 AN: 107521 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 30439

African (AFR) AF: 0.00 AC: 0 AN: 29568

American (AMR) AF: 0.00 AC: 0 AN: 10090

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2595

East Asian (EAS) AF: 0.00 AC: 0 AN: 3386

South Asian (SAS) AF: 0.00 AC: 0 AN: 2465

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5260

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 205

European-Non Finnish (NFE) AF: 0.0000386 AC: 2 AN: 51835

Other (OTH) AF: 0.000688 AC: 1 AN: 1454

Alfa AF: 0.00 Hom.: 636

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.22

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: rs34087972; hg19: chrX-106171158;