rs146792467

chr14-77304845-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_013382.7(POMT2):c.439-45C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00437 in 1,552,670 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0032 (2 hom., cov: 33)
  • Exomes 𝑓: 0.0045 (23 hom.)
• Consequence: POMT2 NM_013382.7 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.359

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 14-77304845-G-A is Benign according to our data. Variant chr14-77304845-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 260301.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-77304845-G-A is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00321 (489/152370) while in subpopulation NFE AF= 0.00514 (350/68036). AF 95% confidence interval is 0.0047. There are 2 homozygotes in gnomad4. There are 210 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POMT2	NM_013382.7	c.439-45C>T		intron_variant		ENST00000261534.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POMT2	ENST00000261534.9	c.439-45C>T		intron_variant		1	NM_013382.7	P1

Frequencies

GnomAD3 genomes AF: 0.00321 AC: 488 AN: 152252 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.00104

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00190

Gnomad ASJ AF: 0.0104

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00331

Gnomad FIN AF: 0.000376

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00514

Gnomad OTH AF: 0.00334

GnomAD3 exomes AF: 0.00363 AC: 582 AN: 160402 Hom.: 5 AF XY: 0.00374 AC XY: 316 AN XY: 84480

Gnomad AFR exome AF: 0.00107

Gnomad AMR exome AF: 0.00246

Gnomad ASJ exome AF: 0.0129

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00427

Gnomad FIN exome AF: 0.000451

Gnomad NFE exome AF: 0.00436

Gnomad OTH exome AF: 0.00512

GnomAD4 exome AF: 0.00449 AC: 6290 AN: 1400300 Hom.: 23 Cov.: 31 AF XY: 0.00448 AC XY: 3093 AN XY: 690946

Gnomad4 AFR exome AF: 0.000685

Gnomad4 AMR exome AF: 0.00249

Gnomad4 ASJ exome AF: 0.0113

Gnomad4 EAS exome AF: 0.0000274

Gnomad4 SAS exome AF: 0.00505

Gnomad4 FIN exome AF: 0.000528

Gnomad4 NFE exome AF: 0.00473

Gnomad4 OTH exome AF: 0.00530

GnomAD4 genome AF: 0.00321 AC: 489 AN: 152370 Hom.: 2 Cov.: 33 AF XY: 0.00282 AC XY: 210 AN XY: 74518

Gnomad4 AFR AF: 0.00103

Gnomad4 AMR AF: 0.00189

Gnomad4 ASJ AF: 0.0104

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.00352

Gnomad4 FIN AF: 0.000376

Gnomad4 NFE AF: 0.00514

Gnomad4 OTH AF: 0.00331

Alfa AF: 0.00490 Hom.: 3

Bravo AF: 0.00323

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	2.1
Dann	Benign	0.38
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: rs146792467; hg19: chr14-77771188;