rs35207939

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_032806.6(POMGNT2):c.1488C>T(p.Gly496Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0143 in 1,613,972 control chromosomes in the GnomAD database, including 208 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0096 ( 11 hom., cov: 33)

Exomes 𝑓: 0.015 ( 197 hom. )

Consequence

POMGNT2
NM_032806.6 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.789

Publications

3 publications found

Variant links:

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]

POMGNT2 Gene-Disease associations (from GenCC):

muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 8
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
myopathy caused by variation in POMGNT2
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
muscular dystrophy-dystroglycanopathy, type A
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

POMGNT2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 3-43079944-G-A is Benign according to our data. Variant chr3-43079944-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 262105.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.789 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00965 (1470/152334) while in subpopulation NFE AF = 0.0156 (1063/68030). AF 95% confidence interval is 0.0148. There are 11 homozygotes in GnomAd4. There are 681 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POMGNT2	NM_032806.6 link	c.1488C>T	p.Gly496Gly	synonymous_variant	Exon 2 of 2	ENST00000344697.3	NP_116195.2	Q8NAT1A0A024R2P4
POMGNT2	NM_001437285.1 link	c.1488C>T	p.Gly496Gly	synonymous_variant	Exon 3 of 3		NP_001424214.1
POMGNT2	XM_011534163.3 link	c.1488C>T	p.Gly496Gly	synonymous_variant	Exon 3 of 3		XP_011532465.1	Q8NAT1A0A024R2P4
POMGNT2	XM_017007353.2 link	c.1488C>T	p.Gly496Gly	synonymous_variant	Exon 4 of 4		XP_016862842.1	Q8NAT1A0A024R2P4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POMGNT2	ENST00000344697.3 link	c.1488C>T	p.Gly496Gly	synonymous_variant	Exon 2 of 2	1	NM_032806.6	ENSP00000344125.2		Q8NAT1

Frequencies

GnomAD3 genomes

AF:

0.00966

AC:

1470

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00270

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.00399

Gnomad ASJ

AF:

0.00778

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00165

Gnomad FIN

AF:

0.0172

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0156

Gnomad OTH

AF:

0.00623

GnomAD2 exomes

AF:

0.0103

AC:

2573

AN:

250656

AF XY:

0.0102

show subpopulations

Gnomad AFR exome

AF:

0.00241

Gnomad AMR exome

AF:

0.00304

Gnomad ASJ exome

AF:

0.00828

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0144

Gnomad NFE exome

AF:

0.0172

Gnomad OTH exome

AF:

0.00850

GnomAD4 exome

AF:

0.0148

AC:

21681

AN:

1461638

Hom.:

197

Cov.:

AF XY:

0.0144

AC XY:

10451

AN XY:

727134

show subpopulations

African (AFR)

AF:

0.00266

AC:

AN:

33480

American (AMR)

AF:

0.00320

AC:

143

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00769

AC:

201

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00158

AC:

136

AN:

86254

European-Finnish (FIN)

AF:

0.0149

AC:

793

AN:

53190

Middle Eastern (MID)

AF:

0.000520

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0177

AC:

19722

AN:

1112004

Other (OTH)

AF:

0.00984

AC:

594

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

1405

2810

4216

5621

7026

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

754

1508

2262

3016

3770

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00965

AC:

1470

AN:

152334

Hom.:

Cov.:

AF XY:

0.00914

AC XY:

681

AN XY:

74494

show subpopulations

African (AFR)

AF:

0.00269

AC:

112

AN:

41570

American (AMR)

AF:

0.00398

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00778

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00166

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.0172

AC:

183

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0156

AC:

1063

AN:

68030

Other (OTH)

AF:

0.00616

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

156

233

311

389

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0134

Hom.:

Bravo

AF:

0.00886

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.0129

EpiControl

AF:

0.0157

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Sep 19, 2016

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Jul 31, 2019

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

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

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 8;C4748320:Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 8

Benign:1

Jul 08, 2021

Fulgent Genetics, Fulgent Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.19

(source)

DANN

Benign

0.63

PhyloP100

-0.79

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over