chrX-106927946-CAT-C

Variant names:

• chrX-106927946-CAT-C
• rs72466477
• NM_020384.4:c.-178-104_-178-103delAT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_020384.4(CLDN2):​c.-178-104_-178-103delAT 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
• 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: Benign. The variant received -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 VariationId 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.

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.-178-104_-178-103delAT		intron	N/A	NP_065117.1	P57739
	CLDN2	NM_001171092.1		c.-178-104_-178-103delAT		intron	N/A	NP_001164563.1	P57739
	CLDN2	NM_001171095.2		c.-178-104_-178-103delAT		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.-178-104_-178-103delAT		intron	N/A	ENSP00000336571.1	P57739
	CLDN2	ENST00000540876.1	TSL:1	c.-178-104_-178-103delAT		intron	N/A	ENSP00000443230.1	P57739
	CLDN2	ENST00000541806.6	TSL:1	c.-178-104_-178-103delAT		intron	N/A	ENSP00000441283.1	P57739

Frequencies

GnomAD3 genomes AF: 0.165 AC: 18185 AN: 110421 Hom.: 1563 Cov.: 19

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

African (AFR) AF: 0.0586 AC: 237 AN: 4046

American (AMR) AF: 0.441 AC: 2228 AN: 5053

Ashkenazi Jewish (ASJ) AF: 0.276 AC: 1261 AN: 4572

East Asian (EAS) AF: 0.566 AC: 6626 AN: 11702

South Asian (SAS) AF: 0.181 AC: 303 AN: 1675

European-Finnish (FIN) AF: 0.140 AC: 1304 AN: 9315

Middle Eastern (MID) AF: 0.231 AC: 137 AN: 594

European-Non Finnish (NFE) AF: 0.153 AC: 13001 AN: 85164

Other (OTH) AF: 0.199 AC: 1786 AN: 8954

GnomAD4 genome AF: 0.164 AC: 18168 AN: 110466 Hom.: 1563 Cov.: 19 AF XY: 0.166 AC XY: 5482 AN XY: 32988

African (AFR) AF: 0.0553 AC: 1684 AN: 30441

American (AMR) AF: 0.379 AC: 3938 AN: 10395

Ashkenazi Jewish (ASJ) AF: 0.274 AC: 724 AN: 2642

East Asian (EAS) AF: 0.524 AC: 1796 AN: 3425

South Asian (SAS) AF: 0.180 AC: 465 AN: 2580

European-Finnish (FIN) AF: 0.127 AC: 728 AN: 5730

Middle Eastern (MID) AF: 0.170 AC: 36 AN: 212

European-Non Finnish (NFE) AF: 0.159 AC: 8431 AN: 52871

Other (OTH) AF: 0.204 AC: 306 AN: 1498

Alfa AF: 0.157 Hom.: 826

Asia WGS AF: 0.303 AC: 762 AN: 2520

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.4
Mutation Taster		=94/6	polymorphism

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: rs72466477; hg19: chrX-106171176;