rs71413457

chr14-77280504-C-G

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.1654-41G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0203 in 1,613,826 control chromosomes in the GnomAD database, including 407 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.016 (31 hom., cov: 33)
  • Exomes 𝑓: 0.021 (376 hom.)
• Consequence: POMT2 NM_013382.7 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.482

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 14-77280504-C-G is Benign according to our data. Variant chr14-77280504-C-G is described in ClinVar as [Benign]. Clinvar id is 260296.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-77280504-C-G is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.016 (2437/152310) while in subpopulation AMR AF= 0.0234 (358/15306). AF 95% confidence interval is 0.0223. There are 31 homozygotes in gnomad4. There are 1119 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 31 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POMT2	NM_013382.7	c.1654-41G>C		intron_variant		ENST00000261534.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POMT2	ENST00000261534.9	c.1654-41G>C		intron_variant		1	NM_013382.7	P1

Frequencies

GnomAD3 genomes AF: 0.0160 AC: 2436 AN: 152192 Hom.: 31 Cov.: 33

Gnomad AFR AF: 0.00444

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.0234

Gnomad ASJ AF: 0.0470

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00600

Gnomad FIN AF: 0.00565

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0232

Gnomad OTH AF: 0.0234

GnomAD3 exomes AF: 0.0167 AC: 4179 AN: 250784 Hom.: 56 AF XY: 0.0168 AC XY: 2278 AN XY: 135598

Gnomad AFR exome AF: 0.00431

Gnomad AMR exome AF: 0.0149

Gnomad ASJ exome AF: 0.0495

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00448

Gnomad FIN exome AF: 0.00664

Gnomad NFE exome AF: 0.0237

Gnomad OTH exome AF: 0.0211

GnomAD4 exome AF: 0.0207 AC: 30319 AN: 1461516 Hom.: 376 Cov.: 36 AF XY: 0.0203 AC XY: 14726 AN XY: 727076

Gnomad4 AFR exome AF: 0.00376

Gnomad4 AMR exome AF: 0.0154

Gnomad4 ASJ exome AF: 0.0506

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00478

Gnomad4 FIN exome AF: 0.00659

Gnomad4 NFE exome AF: 0.0235

Gnomad4 OTH exome AF: 0.0209

GnomAD4 genome AF: 0.0160 AC: 2437 AN: 152310 Hom.: 31 Cov.: 33 AF XY: 0.0150 AC XY: 1119 AN XY: 74468

Gnomad4 AFR AF: 0.00443

Gnomad4 AMR AF: 0.0234

Gnomad4 ASJ AF: 0.0470

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00601

Gnomad4 FIN AF: 0.00565

Gnomad4 NFE AF: 0.0233

Gnomad4 OTH AF: 0.0232

Alfa AF: 0.0213 Hom.: 7

Bravo AF: 0.0175

Asia WGS AF: 0.00606 AC: 21 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

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	5.8
Dann	Benign	0.40

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: rs71413457; hg19: chr14-77746847;