rs138488805

Positions:

• chr14-77277499-T-C

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.2148-18A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00522 in 1,580,396 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0035 (2 hom., cov: 33)
  • Exomes 𝑓: 0.0054 (27 hom.)
• Consequence: POMT2 NM_013382.7 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -1.07

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 14-77277499-T-C is Benign according to our data. Variant chr14-77277499-T-C is described in ClinVar as [Benign]. Clinvar id is 138787.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-77277499-T-C is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0035 (533/152260) while in subpopulation SAS AF= 0.00705 (34/4820). AF 95% confidence interval is 0.00559. There are 2 homozygotes in gnomad4. There are 257 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POMT2	NM_013382.7	c.2148-18A>G		intron_variant		ENST00000261534.9	NP_037514.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POMT2	ENST00000261534.9	c.2148-18A>G		intron_variant		1	NM_013382.7	ENSP00000261534.4

Frequencies

GnomAD3 genomes AF: 0.00350 AC: 533 AN: 152142 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.00106

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00111

Gnomad ASJ AF: 0.00288

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00705

Gnomad FIN AF: 0.00113

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00607

Gnomad OTH AF: 0.000956

GnomAD3 exomes AF: 0.00413 AC: 1036 AN: 250806 Hom.: 6 AF XY: 0.00439 AC XY: 595 AN XY: 135662

Gnomad AFR exome AF: 0.000862

Gnomad AMR exome AF: 0.00116

Gnomad ASJ exome AF: 0.00119

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00797

Gnomad FIN exome AF: 0.000786

Gnomad NFE exome AF: 0.00608

Gnomad OTH exome AF: 0.00342

GnomAD4 exome AF: 0.00540 AC: 7710 AN: 1428136 Hom.: 27 Cov.: 27 AF XY: 0.00540 AC XY: 3847 AN XY: 712424

Gnomad4 AFR exome AF: 0.000827

Gnomad4 AMR exome AF: 0.00121

Gnomad4 ASJ exome AF: 0.00189

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00817

Gnomad4 FIN exome AF: 0.00107

Gnomad4 NFE exome AF: 0.00611

Gnomad4 OTH exome AF: 0.00359

GnomAD4 genome AF: 0.00350 AC: 533 AN: 152260 Hom.: 2 Cov.: 33 AF XY: 0.00345 AC XY: 257 AN XY: 74454

Gnomad4 AFR AF: 0.00106

Gnomad4 AMR AF: 0.00111

Gnomad4 ASJ AF: 0.00288

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00705

Gnomad4 FIN AF: 0.00113

Gnomad4 NFE AF: 0.00607

Gnomad4 OTH AF: 0.000946

Alfa AF: 0.00316 Hom.: 0

Bravo AF: 0.00342

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 14, 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

Likely benign, no assertion criteria provided

clinical testing

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.22
DANN	Benign	0.36

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs138488805; hg19: chr14-77743842;