rs2270420

chr14-77320520-C-Achr14-77320520-C-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_013382.7(POMT2):c.162G>T(p.Ala54=) 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 (★★). Synonymous variant affecting the same amino acid position (i.e. A54A) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.058 (390 hom., cov: 32)
  • Exomes 𝑓: 0.068 (3987 hom.)
• Consequence: POMT2 NM_013382.7 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:11
• Conservation: PhyloP100: 0.256

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]

ACMG classification

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	UniProt
POMT2	NM_013382.7	c.162G>T	p.Ala54=	synonymous_variant	1/21	ENST00000261534.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POMT2	ENST00000261534.9	c.162G>T	p.Ala54=	synonymous_variant	1/21	1	NM_013382.7	P1

Frequencies

GnomAD3 genomes AF: 0.0579 AC: 8814 AN: 152188 Hom.: 391 Cov.: 32

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

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.: 31 AF XY: 0.0687 AC XY: 47624 AN XY: 693278

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.: 32 AF XY: 0.0614 AC XY: 4576 AN XY: 74474

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:11

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:8

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	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	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
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, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Jul 26, 2017	- -

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

Invitae

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. -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

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

Other links and lift over

dbSNP: rs2270420; hg19: chr14-77786863; COSMIC: COSV53623081; COSMIC: COSV53623081;