rs66502123

chr14-77306486-A-G

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.334-45T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 1,602,448 control chromosomes in the GnomAD database, including 11,093 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.087 (735 hom., cov: 32)
  • Exomes 𝑓: 0.11 (10358 hom.)
• Consequence: POMT2 NM_013382.7 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.561

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=-0.71).
• BP6: Variant 14-77306486-A-G is Benign according to our data. Variant chr14-77306486-A-G is described in ClinVar as [Benign]. Clinvar id is 260300.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-77306486-A-G is described in Lovd as [Likely_benign]. Variant chr14-77306486-A-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.179 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POMT2	NM_013382.7	c.334-45T>C		intron_variant		ENST00000261534.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POMT2	ENST00000261534.9	c.334-45T>C		intron_variant		1	NM_013382.7	P1

Frequencies

GnomAD3 genomes AF: 0.0875 AC: 13310 AN: 152158 Hom.: 735 Cov.: 32

Gnomad AFR AF: 0.0334

Gnomad AMI AF: 0.121

Gnomad AMR AF: 0.0661

Gnomad ASJ AF: 0.124

Gnomad EAS AF: 0.00848

Gnomad SAS AF: 0.188

Gnomad FIN AF: 0.0955

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.120

Gnomad OTH AF: 0.0865

GnomAD3 exomes AF: 0.104 AC: 25729 AN: 246266 Hom.: 1708 AF XY: 0.113 AC XY: 15024 AN XY: 133314

Gnomad AFR exome AF: 0.0304

Gnomad AMR exome AF: 0.0471

Gnomad ASJ exome AF: 0.129

Gnomad EAS exome AF: 0.00539

Gnomad SAS exome AF: 0.194

Gnomad FIN exome AF: 0.101

Gnomad NFE exome AF: 0.123

Gnomad OTH exome AF: 0.102

GnomAD4 exome AF: 0.113 AC: 164574 AN: 1450172 Hom.: 10358 Cov.: 29 AF XY: 0.117 AC XY: 84298 AN XY: 721308

Gnomad4 AFR exome AF: 0.0274

Gnomad4 AMR exome AF: 0.0489

Gnomad4 ASJ exome AF: 0.131

Gnomad4 EAS exome AF: 0.00466

Gnomad4 SAS exome AF: 0.192

Gnomad4 FIN exome AF: 0.0988

Gnomad4 NFE exome AF: 0.117

Gnomad4 OTH exome AF: 0.113

GnomAD4 genome AF: 0.0874 AC: 13312 AN: 152276 Hom.: 735 Cov.: 32 AF XY: 0.0886 AC XY: 6593 AN XY: 74452

Gnomad4 AFR AF: 0.0334

Gnomad4 AMR AF: 0.0658

Gnomad4 ASJ AF: 0.124

Gnomad4 EAS AF: 0.00850

Gnomad4 SAS AF: 0.189

Gnomad4 FIN AF: 0.0955

Gnomad4 NFE AF: 0.120

Gnomad4 OTH AF: 0.0856

Alfa AF: 0.105 Hom.: 215

Bravo AF: 0.0784

Asia WGS AF: 0.117 AC: 411 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

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	-0.71
Cadd	Benign	14
Dann	Benign	0.86

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs66502123; hg19: chr14-77772829;