rs7153929

Positions:

• chr14-77291400-G-A
• chr14-77291400-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_013382.7(POMT2):​c.1117-20C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 578,046 control chromosomes in the GnomAD database, including 3,351 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (1264 hom., cov: 21)
  • Exomes 𝑓: 0.11 (2087 hom.)
• Consequence: POMT2 NM_013382.7 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -1.21

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 14-77291400-G-A is Benign according to our data. Variant chr14-77291400-G-A is described in ClinVar as [Benign]. Clinvar id is 95533.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-77291400-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.277 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POMT2	NM_013382.7	c.1117-20C>T		intron_variant		ENST00000261534.9	NP_037514.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POMT2	ENST00000261534.9	c.1117-20C>T		intron_variant		1	NM_013382.7	ENSP00000261534	P1

Frequencies

GnomAD3 genomes AF: 0.113 AC: 13059 AN: 115916 Hom.: 1264 Cov.: 21

Gnomad AFR AF: 0.282

Gnomad AMI AF: 0.0718

Gnomad AMR AF: 0.0733

Gnomad ASJ AF: 0.0605

Gnomad EAS AF: 0.000322

Gnomad SAS AF: 0.0687

Gnomad FIN AF: 0.0869

Gnomad MID AF: 0.122

Gnomad NFE AF: 0.0411

Gnomad OTH AF: 0.111

GnomAD3 exomes AF: 0.0648 AC: 11401 AN: 175986 Hom.: 823 AF XY: 0.0614 AC XY: 5894 AN XY: 96020

Gnomad AFR exome AF: 0.313

Gnomad AMR exome AF: 0.0385

Gnomad ASJ exome AF: 0.0583

Gnomad EAS exome AF: 0.000439

Gnomad SAS exome AF: 0.0629

Gnomad FIN exome AF: 0.0611

Gnomad NFE exome AF: 0.0477

Gnomad OTH exome AF: 0.0580

GnomAD4 exome AF: 0.115 AC: 53027 AN: 462044 Hom.: 2087 Cov.: 9 AF XY: 0.109 AC XY: 26728 AN XY: 245522

Gnomad4 AFR exome AF: 0.406

Gnomad4 AMR exome AF: 0.0484

Gnomad4 ASJ exome AF: 0.0994

Gnomad4 EAS exome AF: 0.000608

Gnomad4 SAS exome AF: 0.0667

Gnomad4 FIN exome AF: 0.0807

Gnomad4 NFE exome AF: 0.121

Gnomad4 OTH exome AF: 0.130

GnomAD4 genome AF: 0.113 AC: 13078 AN: 116002 Hom.: 1264 Cov.: 21 AF XY: 0.115 AC XY: 6145 AN XY: 53358

Gnomad4 AFR AF: 0.282

Gnomad4 AMR AF: 0.0732

Gnomad4 ASJ AF: 0.0605

Gnomad4 EAS AF: 0.000322

Gnomad4 SAS AF: 0.0690

Gnomad4 FIN AF: 0.0869

Gnomad4 NFE AF: 0.0411

Gnomad4 OTH AF: 0.110

Alfa AF: 0.0597 Hom.: 97

Bravo AF: 0.106

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:6

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jul 18, 2012	- -
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+	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 28, 2014	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

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

Jan 31, 2024

- -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.43
DANN	Benign	0.25

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: rs7153929; hg19: chr14-77757743;