rs2936818

chr3-43081474-G-Achr3-43081474-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_032806.6(POMGNT2):c.-43C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.469 in 1,460,022 control chromosomes in the GnomAD database, including 163,239 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.42 (14588 hom., cov: 33)
  • Exomes 𝑓: 0.47 (148651 hom.)
• Consequence: POMGNT2 NM_032806.6 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.605

Genes affected

POMGNT2 (HGNC:25902): (protein O-linked mannose N-acetylglucosaminyltransferase 2 (beta 1,4-)) This gene encodes a protein with glycosyltransferase activity although its function is not currently known. [provided by RefSeq, Sep 2012]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 3-43081474-G-A is Benign according to our data. Variant chr3-43081474-G-A is described in ClinVar as [Benign]. Clinvar id is 262102.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-43081474-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.605 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POMGNT2	NM_032806.6	c.-43C>T		5_prime_UTR_variant	2/2	ENST00000344697.3
POMGNT2	XM_005265515.4	c.-43C>T		5_prime_UTR_variant	3/3
POMGNT2	XM_011534163.3	c.-43C>T		5_prime_UTR_variant	3/3
POMGNT2	XM_017007353.2	c.-43C>T		5_prime_UTR_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POMGNT2	ENST00000344697.3	c.-43C>T		5_prime_UTR_variant	2/2	1	NM_032806.6	P1

Frequencies

GnomAD3 genomes AF: 0.425 AC: 64548 AN: 151926 Hom.: 14578 Cov.: 33

Gnomad AFR AF: 0.273

Gnomad AMI AF: 0.498

Gnomad AMR AF: 0.555

Gnomad ASJ AF: 0.511

Gnomad EAS AF: 0.623

Gnomad SAS AF: 0.466

Gnomad FIN AF: 0.388

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.469

Gnomad OTH AF: 0.456

GnomAD3 exomes AF: 0.491 AC: 50306 AN: 102478 Hom.: 12693 AF XY: 0.492 AC XY: 26168 AN XY: 53142

Gnomad AFR exome AF: 0.265

Gnomad AMR exome AF: 0.619

Gnomad ASJ exome AF: 0.530

Gnomad EAS exome AF: 0.629

Gnomad SAS exome AF: 0.473

Gnomad FIN exome AF: 0.395

Gnomad NFE exome AF: 0.480

Gnomad OTH exome AF: 0.492

GnomAD4 exome AF: 0.474 AC: 619935 AN: 1307978 Hom.: 148651 Cov.: 24 AF XY: 0.474 AC XY: 302012 AN XY: 637480

Gnomad4 AFR exome AF: 0.266

Gnomad4 AMR exome AF: 0.599

Gnomad4 ASJ exome AF: 0.512

Gnomad4 EAS exome AF: 0.608

Gnomad4 SAS exome AF: 0.456

Gnomad4 FIN exome AF: 0.390

Gnomad4 NFE exome AF: 0.476

Gnomad4 OTH exome AF: 0.477

GnomAD4 genome AF: 0.425 AC: 64585 AN: 152044 Hom.: 14588 Cov.: 33 AF XY: 0.426 AC XY: 31692 AN XY: 74314

Gnomad4 AFR AF: 0.273

Gnomad4 AMR AF: 0.555

Gnomad4 ASJ AF: 0.511

Gnomad4 EAS AF: 0.623

Gnomad4 SAS AF: 0.465

Gnomad4 FIN AF: 0.388

Gnomad4 NFE AF: 0.469

Gnomad4 OTH AF: 0.453

Alfa AF: 0.453 Hom.: 12995

Bravo AF: 0.434

Asia WGS AF: 0.520 AC: 1809 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 11, 2016	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. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 8 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Oct 25, 2021

- -

Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 8 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Oct 25, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	6.8
Dann	Benign	0.78

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: rs2936818; hg19: chr3-43122966; COSMIC: COSV60953666;