Variant rs2270420 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_013382.7(POMT2):c.162G>T(p.Ala54Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0673 in 1,553,826 control chromosomes in the GnomAD database, including 4,377 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.058 ( 390 hom., cov: 32)

Exomes 𝑓: 0.068 ( 3987 hom. )

Consequence

POMT2
NM_013382.7 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:12

Conservation

PhyloP100: 0.256

Variant links:

Genes affected

POMT2 (HGNC:19743): (protein O-mannosyltransferase 2) The protein encoded by this gene is an O-mannosyltransferase that requires interaction with the product of the POMT1 gene for enzymatic function. The encoded protein is found in the membrane of the endoplasmic reticulum. Defects in this gene are a cause of Walker-Warburg syndrome (WWS).[provided by RefSeq, Oct 2008]

POMT2 links:

POMT2 (HGNC:):

POMT2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.51).

BP6

Variant 14-77320520-C-A is Benign according to our data. Variant chr14-77320520-C-A is described in ClinVar as [Benign]. Clinvar id is 95536.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-77320520-C-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.256 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.21 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POMT2	NM_013382.7 linkuse as main transcript	c.162G>T	p.Ala54Ala	synonymous_variant	1/21	ENST00000261534.9	NP_037514.2	Q9UKY4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POMT2	ENST00000261534.9 linkuse as main transcript	c.162G>T	p.Ala54Ala	synonymous_variant	1/21	1	NM_013382.7	ENSP00000261534.4		Q9UKY4-1

Frequencies

GnomAD3 genomes

AF:

0.0579

AC:

8814

AN:

152188

Hom.:

391

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0117

Gnomad AMI

AF:

0.0636

Gnomad AMR

AF:

0.0453

Gnomad ASJ

AF:

0.0614

Gnomad EAS

AF:

0.221

Gnomad SAS

AF:

0.0746

Gnomad FIN

AF:

0.114

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.0657

Gnomad OTH

AF:

0.0760

GnomAD3 exomes

AF:

0.0744

AC:

11562

AN:

155460

Hom.:

677

AF XY:

0.0752

AC XY:

6379

AN XY:

84866

show subpopulations

Gnomad AFR exome

AF:

0.0106

Gnomad AMR exome

AF:

0.0326

Gnomad ASJ exome

AF:

0.0667

Gnomad EAS exome

AF:

0.242

Gnomad SAS exome

AF:

0.0748

Gnomad FIN exome

AF:

0.119

Gnomad NFE exome

AF:

0.0642

Gnomad OTH exome

AF:

0.0662

GnomAD4 exome

AF:

0.0684

AC:

95795

AN:

1401520

Hom.:

3987

Cov.:

AF XY:

0.0687

AC XY:

47624

AN XY:

693278

show subpopulations

Gnomad4 AFR exome

AF:

0.00922

Gnomad4 AMR exome

AF:

0.0351

Gnomad4 ASJ exome

AF:

0.0647

Gnomad4 EAS exome

AF:

0.223

Gnomad4 SAS exome

AF:

0.0717

Gnomad4 FIN exome

AF:

0.111

Gnomad4 NFE exome

AF:

0.0642

Gnomad4 OTH exome

AF:

0.0725

GnomAD4 genome

AF:

0.0578

AC:

8805

AN:

152306

Hom.:

390

Cov.:

AF XY:

0.0614

AC XY:

4576

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.0117

Gnomad4 AMR

AF:

0.0452

Gnomad4 ASJ

AF:

0.0614

Gnomad4 EAS

AF:

0.221

Gnomad4 SAS

AF:

0.0741

Gnomad4 FIN

AF:

0.114

Gnomad4 NFE

AF:

0.0657

Gnomad4 OTH

AF:

0.0752

Alfa

AF:

0.0639

Hom.:

382

Bravo

AF:

0.0527

Asia WGS

AF:

0.112

AC:

391

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:12

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:8

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Jan 13, 2015	p.Ala54Ala in exon 1 of POMT2: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue and is not located wit hin the splice consensus sequence. It has been identified in 5.8% (478/8280) of European American chromosomes from a broad population by the NHLBI Exome Sequenc ing Project (http://evs.gs.washington.edu/EVS; dbSNP rs2270420). -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Oct 25, 2012	- -
Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Jul 26, 2017	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A2;C3150416:Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B2;C3150418:Autosomal recessive limb-girdle muscular dystrophy type 2N

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Autosomal recessive limb-girdle muscular dystrophy type 2N

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

5.8

DANN

Benign

0.66

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over