X-106927928-GT-GTTT

Variant names:

• chrX-106927928-G-GTT
• rs34087972
• NM_020384.4:c.-178-114_-178-113dupTT

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_020384.4(CLDN2):​c.-178-114_-178-113dupTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00654 in 189,739 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 28 hemizygotes in GnomAD. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00063 (0 hom., 22 hem., cov: 0)
  • Exomes 𝑓: 0.014 (0 hom. 6 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: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAd4 at 68 AD,Unknown gene.

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.-178-114_-178-113dupTT		intron	N/A	NP_065117.1	P57739
	CLDN2	NM_001171092.1		c.-178-114_-178-113dupTT		intron	N/A	NP_001164563.1	P57739
	CLDN2	NM_001171095.2		c.-178-114_-178-113dupTT		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.-178-123_-178-122insTT		intron	N/A	ENSP00000336571.1	P57739
	CLDN2	ENST00000540876.1	TSL:1	c.-178-123_-178-122insTT		intron	N/A	ENSP00000443230.1	P57739
	CLDN2	ENST00000541806.6	TSL:1	c.-178-123_-178-122insTT		intron	N/A	ENSP00000441283.1	P57739

Frequencies

GnomAD3 genomes AF: 0.000633 AC: 68 AN: 107452 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000542

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000298

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00559

Gnomad SAS AF: 0.00485

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000328

Gnomad OTH AF: 0.000696

GnomAD4 exome AF: 0.0143 AC: 1173 AN: 82279 Hom.: 0 AF XY: 0.000323 AC XY: 6 AN XY: 18599

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

African (AFR) AF: 0.0533 AC: 108 AN: 2027

American (AMR) AF: 0.0344 AC: 95 AN: 2761

Ashkenazi Jewish (ASJ) AF: 0.0123 AC: 36 AN: 2933

East Asian (EAS) AF: 0.0770 AC: 334 AN: 4335

South Asian (SAS) AF: 0.0313 AC: 30 AN: 958

European-Finnish (FIN) AF: 0.00606 AC: 36 AN: 5937

Middle Eastern (MID) AF: 0.00756 AC: 3 AN: 397

European-Non Finnish (NFE) AF: 0.00796 AC: 456 AN: 57255

Other (OTH) AF: 0.0132 AC: 75 AN: 5676

⚠️ 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: 0.000633 AC: 68 AN: 107460 Hom.: 0 Cov.: 0 AF XY: 0.000724 AC XY: 22 AN XY: 30400

African (AFR) AF: 0.000542 AC: 16 AN: 29547

American (AMR) AF: 0.000298 AC: 3 AN: 10076

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2593

East Asian (EAS) AF: 0.00561 AC: 19 AN: 3386

South Asian (SAS) AF: 0.00487 AC: 12 AN: 2464

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5252

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

European-Non Finnish (NFE) AF: 0.000328 AC: 17 AN: 51822

Other (OTH) AF: 0.000689 AC: 1 AN: 1452

Alfa AF: 0.000939 Hom.: 636

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.22
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs34087972; hg19: chrX-106171158;