14-77288187-A-G

Position:

• chr14-77288187-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_013382.7(POMT2):​c.1253+575T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0534 in 152,284 control chromosomes in the GnomAD database, including 272 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.053 (272 hom., cov: 32)
• Consequence: POMT2 NM_013382.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.515

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0738 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POMT2	NM_013382.7	c.1253+575T>C		intron_variant		ENST00000261534.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POMT2	ENST00000261534.9	c.1253+575T>C		intron_variant		1	NM_013382.7	P1

Frequencies

GnomAD3 genomes AF: 0.0534 AC: 8125 AN: 152166 Hom.: 271 Cov.: 32

Gnomad AFR AF: 0.0137

Gnomad AMI AF: 0.0702

Gnomad AMR AF: 0.0537

Gnomad ASJ AF: 0.0783

Gnomad EAS AF: 0.0198

Gnomad SAS AF: 0.0799

Gnomad FIN AF: 0.0602

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0755

Gnomad OTH AF: 0.0574

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0534 AC: 8135 AN: 152284 Hom.: 272 Cov.: 32 AF XY: 0.0536 AC XY: 3994 AN XY: 74468

Gnomad4 AFR AF: 0.0136

Gnomad4 AMR AF: 0.0537

Gnomad4 ASJ AF: 0.0783

Gnomad4 EAS AF: 0.0201

Gnomad4 SAS AF: 0.0800

Gnomad4 FIN AF: 0.0602

Gnomad4 NFE AF: 0.0755

Gnomad4 OTH AF: 0.0634

Alfa AF: 0.0279 Hom.: 18

Bravo AF: 0.0497

Asia WGS AF: 0.0740 AC: 258 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	7.6
DANN	Benign	0.92

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: rs2058916; hg19: chr14-77754530;