X-106927928-GT-GTT

Variant names:

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

Variant summary

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

The NM_020384.4(CLDN2):​c.-178-113dupT 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
• 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-106927928-G-GT is Benign according to our data. Variant chrX-106927928-G-GT is described in ClinVar as Benign. ClinVar VariationId 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.

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

Frequencies

GnomAD3 genomes AF: 0.575 AC: 61697 AN: 107368 Hom.: 14145 Cov.: 0

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

African (AFR) AF: 0.597 AC: 1188 AN: 1991

American (AMR) AF: 0.522 AC: 1395 AN: 2674

Ashkenazi Jewish (ASJ) AF: 0.306 AC: 867 AN: 2830

East Asian (EAS) AF: 0.739 AC: 3173 AN: 4291

South Asian (SAS) AF: 0.484 AC: 436 AN: 900

European-Finnish (FIN) AF: 0.244 AC: 1398 AN: 5725

Middle Eastern (MID) AF: 0.329 AC: 125 AN: 380

European-Non Finnish (NFE) AF: 0.289 AC: 15786 AN: 54688

Other (OTH) AF: 0.347 AC: 1903 AN: 5491

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

African (AFR) AF: 0.813 AC: 23997 AN: 29530

American (AMR) AF: 0.665 AC: 6702 AN: 10073

Ashkenazi Jewish (ASJ) AF: 0.466 AC: 1208 AN: 2595

East Asian (EAS) AF: 0.917 AC: 3102 AN: 3383

South Asian (SAS) AF: 0.707 AC: 1741 AN: 2464

European-Finnish (FIN) AF: 0.375 AC: 1958 AN: 5227

Middle Eastern (MID) AF: 0.356 AC: 73 AN: 205

European-Non Finnish (NFE) AF: 0.424 AC: 21968 AN: 51784

Other (OTH) AF: 0.565 AC: 821 AN: 1453

Alfa AF: 0.212 Hom.: 636

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		0.22
Mutation Taster		=100/0	polymorphism (auto)

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;