rs79509556

chr14-77296305-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_013382.7(POMT2):c.1007-32G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0291 in 1,483,100 control chromosomes in the GnomAD database, including 806 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.020 (37 hom., cov: 31)
  • Exomes 𝑓: 0.030 (769 hom.)
• Consequence: POMT2 NM_013382.7 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.0170

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=-0.8).
• BP6: Variant 14-77296305-C-T is Benign according to our data. Variant chr14-77296305-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 260288.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-77296305-C-T is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.02 (3038/152264) while in subpopulation NFE AF= 0.0319 (2171/68016). AF 95% confidence interval is 0.0308. There are 37 homozygotes in gnomad4. There are 1411 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 37 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POMT2	NM_013382.7	c.1007-32G>A		intron_variant		ENST00000261534.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POMT2	ENST00000261534.9	c.1007-32G>A		intron_variant		1	NM_013382.7	P1

Frequencies

GnomAD3 genomes AF: 0.0200 AC: 3040 AN: 152146 Hom.: 37 Cov.: 31

Gnomad AFR AF: 0.00499

Gnomad AMI AF: 0.0373

Gnomad AMR AF: 0.0156

Gnomad ASJ AF: 0.0222

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.00538

Gnomad FIN AF: 0.0220

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0319

Gnomad OTH AF: 0.0229

GnomAD3 exomes AF: 0.0200 AC: 3525 AN: 175870 Hom.: 54 AF XY: 0.0202 AC XY: 1877 AN XY: 93138

Gnomad AFR exome AF: 0.00528

Gnomad AMR exome AF: 0.0124

Gnomad ASJ exome AF: 0.0201

Gnomad EAS exome AF: 0.0000751

Gnomad SAS exome AF: 0.00660

Gnomad FIN exome AF: 0.0206

Gnomad NFE exome AF: 0.0324

Gnomad OTH exome AF: 0.0261

GnomAD4 exome AF: 0.0302 AC: 40165 AN: 1330836 Hom.: 769 Cov.: 20 AF XY: 0.0294 AC XY: 19510 AN XY: 662784

Gnomad4 AFR exome AF: 0.00453

Gnomad4 AMR exome AF: 0.0134

Gnomad4 ASJ exome AF: 0.0216

Gnomad4 EAS exome AF: 0.0000537

Gnomad4 SAS exome AF: 0.00656

Gnomad4 FIN exome AF: 0.0205

Gnomad4 NFE exome AF: 0.0355

Gnomad4 OTH exome AF: 0.0281

GnomAD4 genome AF: 0.0200 AC: 3038 AN: 152264 Hom.: 37 Cov.: 31 AF XY: 0.0190 AC XY: 1411 AN XY: 74456

Gnomad4 AFR AF: 0.00498

Gnomad4 AMR AF: 0.0156

Gnomad4 ASJ AF: 0.0222

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.00539

Gnomad4 FIN AF: 0.0220

Gnomad4 NFE AF: 0.0319

Gnomad4 OTH AF: 0.0227

Alfa AF: 0.0268 Hom.: 13

Bravo AF: 0.0193

Asia WGS AF: 0.00318 AC: 11 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Nov 29, 2016	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2018

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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	2.6
Dann	Benign	0.85

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: rs79509556; hg19: chr14-77762648;