rs3783986

Positions:

• chr14-77296529-C-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.1007-256G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.419 in 519,272 control chromosomes in the GnomAD database, including 46,553 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.41 (13190 hom., cov: 32)
  • Exomes 𝑓: 0.42 (33363 hom.)
• Consequence: POMT2 NM_013382.7 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.243

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=-0.96).
• BP6: Variant 14-77296529-C-T is Benign according to our data. Variant chr14-77296529-C-T is described in ClinVar as [Benign]. Clinvar id is 683960.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.505 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POMT2	NM_013382.7	c.1007-256G>A		intron_variant		ENST00000261534.9	NP_037514.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POMT2	ENST00000261534.9	c.1007-256G>A		intron_variant		1	NM_013382.7	ENSP00000261534	P1

Frequencies

GnomAD3 genomes AF: 0.414 AC: 62876 AN: 151958 Hom.: 13181 Cov.: 32

Gnomad AFR AF: 0.454

Gnomad AMI AF: 0.398

Gnomad AMR AF: 0.438

Gnomad ASJ AF: 0.494

Gnomad EAS AF: 0.503

Gnomad SAS AF: 0.522

Gnomad FIN AF: 0.339

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.376

Gnomad OTH AF: 0.436

GnomAD4 exome AF: 0.422 AC: 154899 AN: 367196 Hom.: 33363 Cov.: 0 AF XY: 0.428 AC XY: 82243 AN XY: 191940

Gnomad4 AFR exome AF: 0.460

Gnomad4 AMR exome AF: 0.481

Gnomad4 ASJ exome AF: 0.503

Gnomad4 EAS exome AF: 0.504

Gnomad4 SAS exome AF: 0.538

Gnomad4 FIN exome AF: 0.342

Gnomad4 NFE exome AF: 0.388

Gnomad4 OTH exome AF: 0.424

GnomAD4 genome AF: 0.414 AC: 62928 AN: 152076 Hom.: 13190 Cov.: 32 AF XY: 0.417 AC XY: 30997 AN XY: 74332

Gnomad4 AFR AF: 0.454

Gnomad4 AMR AF: 0.438

Gnomad4 ASJ AF: 0.494

Gnomad4 EAS AF: 0.502

Gnomad4 SAS AF: 0.522

Gnomad4 FIN AF: 0.339

Gnomad4 NFE AF: 0.376

Gnomad4 OTH AF: 0.433

Alfa AF: 0.398 Hom.: 16588

Bravo AF: 0.424

Asia WGS AF: 0.520 AC: 1813 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 19, 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	-0.96
CADD	Benign	0.81
DANN	Benign	0.75

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: rs3783986; hg19: chr14-77762872;