rs2302831

chr14-77296129-T-C

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.1116+35A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0219 in 1,479,704 control chromosomes in the GnomAD database, including 507 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 (47 hom., cov: 31)
  • Exomes 𝑓: 0.022 (460 hom.)
• Consequence: POMT2 NM_013382.7 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.00900

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=-0.9).
• BP6: Variant 14-77296129-T-C is Benign according to our data. Variant chr14-77296129-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 260289.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-77296129-T-C is described in Lovd as [Benign].
• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0591 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POMT2	NM_013382.7	c.1116+35A>G		intron_variant		ENST00000261534.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POMT2	ENST00000261534.9	c.1116+35A>G		intron_variant		1	NM_013382.7	P1

Frequencies

GnomAD3 genomes AF: 0.0197 AC: 2997 AN: 152158 Hom.: 47 Cov.: 31

Gnomad AFR AF: 0.00463

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0342

Gnomad ASJ AF: 0.0596

Gnomad EAS AF: 0.0178

Gnomad SAS AF: 0.0470

Gnomad FIN AF: 0.0167

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0219

Gnomad OTH AF: 0.0325

GnomAD3 exomes AF: 0.0267 AC: 4685 AN: 175198 Hom.: 91 AF XY: 0.0280 AC XY: 2582 AN XY: 92374

Gnomad AFR exome AF: 0.00316

Gnomad AMR exome AF: 0.0334

Gnomad ASJ exome AF: 0.0557

Gnomad EAS exome AF: 0.0128

Gnomad SAS exome AF: 0.0446

Gnomad FIN exome AF: 0.0174

Gnomad NFE exome AF: 0.0224

Gnomad OTH exome AF: 0.0358

GnomAD4 exome AF: 0.0221 AC: 29353 AN: 1327426 Hom.: 460 Cov.: 20 AF XY: 0.0233 AC XY: 15371 AN XY: 660650

Gnomad4 AFR exome AF: 0.00357

Gnomad4 AMR exome AF: 0.0332

Gnomad4 ASJ exome AF: 0.0574

Gnomad4 EAS exome AF: 0.0210

Gnomad4 SAS exome AF: 0.0473

Gnomad4 FIN exome AF: 0.0172

Gnomad4 NFE exome AF: 0.0193

Gnomad4 OTH exome AF: 0.0261

GnomAD4 genome AF: 0.0196 AC: 2992 AN: 152278 Hom.: 47 Cov.: 31 AF XY: 0.0205 AC XY: 1530 AN XY: 74466

Gnomad4 AFR AF: 0.00459

Gnomad4 AMR AF: 0.0341

Gnomad4 ASJ AF: 0.0596

Gnomad4 EAS AF: 0.0176

Gnomad4 SAS AF: 0.0466

Gnomad4 FIN AF: 0.0167

Gnomad4 NFE AF: 0.0219

Gnomad4 OTH AF: 0.0317

Alfa AF: 0.0268 Hom.: 12

Bravo AF: 0.0187

Asia WGS AF: 0.0280 AC: 97 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

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

Jul 15, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	1.1
Dann	Benign	0.34
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs2302831; hg19: chr14-77762472;