rs438931

chr14-77279967-G-Achr14-77279967-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.1786-39C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 1,613,896 control chromosomes in the GnomAD database, including 16,685 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (1419 hom., cov: 32)
  • Exomes 𝑓: 0.14 (15266 hom.)
• Consequence: POMT2 NM_013382.7 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.517

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=-0.82).
• BP6: Variant 14-77279967-G-A is Benign according to our data. Variant chr14-77279967-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 260297.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-77279967-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.313 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POMT2	NM_013382.7	c.1786-39C>T		intron_variant		ENST00000261534.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POMT2	ENST00000261534.9	c.1786-39C>T		intron_variant		1	NM_013382.7	P1

Frequencies

GnomAD3 genomes AF: 0.130 AC: 19799 AN: 152028 Hom.: 1416 Cov.: 32

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.239

Gnomad AMR AF: 0.153

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.325

Gnomad SAS AF: 0.143

Gnomad FIN AF: 0.0925

Gnomad MID AF: 0.124

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.141

GnomAD3 exomes AF: 0.146 AC: 36673 AN: 251062 Hom.: 3143 AF XY: 0.144 AC XY: 19599 AN XY: 135728

Gnomad AFR exome AF: 0.108

Gnomad AMR exome AF: 0.134

Gnomad ASJ exome AF: 0.168

Gnomad EAS exome AF: 0.345

Gnomad SAS exome AF: 0.147

Gnomad FIN exome AF: 0.0985

Gnomad NFE exome AF: 0.130

Gnomad OTH exome AF: 0.138

GnomAD4 exome AF: 0.138 AC: 202199 AN: 1461750 Hom.: 15266 Cov.: 35 AF XY: 0.138 AC XY: 100253 AN XY: 727170

Gnomad4 AFR exome AF: 0.107

Gnomad4 AMR exome AF: 0.142

Gnomad4 ASJ exome AF: 0.168

Gnomad4 EAS exome AF: 0.341

Gnomad4 SAS exome AF: 0.142

Gnomad4 FIN exome AF: 0.0997

Gnomad4 NFE exome AF: 0.132

Gnomad4 OTH exome AF: 0.146

GnomAD4 genome AF: 0.130 AC: 19812 AN: 152146 Hom.: 1419 Cov.: 32 AF XY: 0.131 AC XY: 9774 AN XY: 74372

Gnomad4 AFR AF: 0.106

Gnomad4 AMR AF: 0.152

Gnomad4 ASJ AF: 0.164

Gnomad4 EAS AF: 0.326

Gnomad4 SAS AF: 0.143

Gnomad4 FIN AF: 0.0925

Gnomad4 NFE AF: 0.127

Gnomad4 OTH AF: 0.140

Alfa AF: 0.134 Hom.: 1998

Bravo AF: 0.135

Asia WGS AF: 0.199 AC: 694 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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- -

not provided Benign:1

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	-0.82
Cadd	Benign	0.98
Dann	Benign	0.83

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: rs438931; hg19: chr14-77746310; COSMIC: COSV55070239; COSMIC: COSV55070239;