14-77285582-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_013382.7(POMT2):c.1383G>A(p.Arg461Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.807 in 1,613,592 control chromosomes in the GnomAD database, including 526,782 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.83 ( 52375 hom., cov: 31)

Exomes 𝑓: 0.80 ( 474407 hom. )

Consequence

POMT2
NM_013382.7 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: 0.0250

Publications

27 publications found

Variant links:

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]

POMT2 Gene-Disease associations (from GenCC):

muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A2
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
myopathy caused by variation in POMT2
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B2
Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics
autosomal recessive limb-girdle muscular dystrophy type 2N
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
congenital muscular dystrophy with cerebellar involvement
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
congenital muscular dystrophy with intellectual disability
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
muscle-eye-brain disease
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
muscular dystrophy-dystroglycanopathy, type A
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

POMT2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.38).

BP6

Variant 14-77285582-C-T is Benign according to our data. Variant chr14-77285582-C-T is described in ClinVar as Benign. ClinVar VariationId is 166906.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.025 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.929 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POMT2	NM_013382.7 link	c.1383G>A	p.Arg461Arg	synonymous_variant	Exon 13 of 21	ENST00000261534.9	NP_037514.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POMT2	ENST00000261534.9 link	c.1383G>A	p.Arg461Arg	synonymous_variant	Exon 13 of 21	1	NM_013382.7	ENSP00000261534.4

Frequencies

GnomAD3 genomes

AF:

0.829

AC:

125885

AN:

151936

Hom.:

52327

Cov.:

show subpopulations

Gnomad AFR

AF:

0.868

Gnomad AMI

AF:

0.850

Gnomad AMR

AF:

0.762

Gnomad ASJ

AF:

0.855

Gnomad EAS

AF:

0.951

Gnomad SAS

AF:

0.804

Gnomad FIN

AF:

0.856

Gnomad MID

AF:

0.763

Gnomad NFE

AF:

0.806

Gnomad OTH

AF:

0.838

GnomAD2 exomes

AF:

0.818

AC:

205702

AN:

251466

AF XY:

0.818

show subpopulations

Gnomad AFR exome

AF:

0.875

Gnomad AMR exome

AF:

0.734

Gnomad ASJ exome

AF:

0.848

Gnomad EAS exome

AF:

0.963

Gnomad FIN exome

AF:

0.844

Gnomad NFE exome

AF:

0.809

Gnomad OTH exome

AF:

0.815

GnomAD4 exome

AF:

0.805

AC:

1176143

AN:

1461538

Hom.:

474407

Cov.:

AF XY:

0.805

AC XY:

585076

AN XY:

727094

show subpopulations

African (AFR)

AF:

0.874

AC:

29243

AN:

33472

American (AMR)

AF:

0.744

AC:

33289

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.852

AC:

22257

AN:

26134

East Asian (EAS)

AF:

0.967

AC:

38374

AN:

39698

South Asian (SAS)

AF:

0.795

AC:

68594

AN:

86254

European-Finnish (FIN)

AF:

0.842

AC:

44970

AN:

53418

Middle Eastern (MID)

AF:

0.800

AC:

4616

AN:

5768

European-Non Finnish (NFE)

AF:

0.797

AC:

885592

AN:

1111678

Other (OTH)

AF:

0.815

AC:

49208

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

14331

28662

42992

57323

71654

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20748

41496

62244

82992

103740

<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:

0.829

AC:

125986

AN:

152054

Hom.:

52375

Cov.:

AF XY:

0.830

AC XY:

61685

AN XY:

74322

show subpopulations

African (AFR)

AF:

0.868

AC:

36009

AN:

41472

American (AMR)

AF:

0.762

AC:

11632

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.855

AC:

2968

AN:

3470

East Asian (EAS)

AF:

0.951

AC:

4904

AN:

5154

South Asian (SAS)

AF:

0.804

AC:

3870

AN:

4814

European-Finnish (FIN)

AF:

0.856

AC:

9032

AN:

10556

Middle Eastern (MID)

AF:

0.762

AC:

224

AN:

294

European-Non Finnish (NFE)

AF:

0.806

AC:

54798

AN:

67998

Other (OTH)

AF:

0.841

AC:

1777

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1109

2217

3326

4434

5543

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

884

1768

2652

3536

4420

<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:

0.813

Hom.:

79296

Bravo

AF:

0.825

Asia WGS

AF:

0.886

AC:

3082

AN:

3478

EpiCase

AF:

0.805

EpiControl

AF:

0.806

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Jun 11, 2013

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Nov 24, 2014

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Arg461Arg in exon 13 of POMT2: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue and is not located wit hin the splice consensus sequence. It has been identified in 19.3% (1664/8600) o f European American chromosomes from a broad population by the NHLBI Exome Seque ncing Project (http://evs.gs.washington.edu/EVS; dbSNP rs2270419). -

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A2;C3150416:Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B2;C3150418:Autosomal recessive limb-girdle muscular dystrophy type 2N

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 intellectual disability), type B2

Benign:1

Oct 25, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Autosomal recessive limb-girdle muscular dystrophy type 2N

Benign:1

Oct 25, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

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 A2

Benign:1

Oct 25, 2021

Genome-Nilou Lab

Significance: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

-0.38

CADD

Benign

(source)

DANN

Benign

0.83

PhyloP100

0.025

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism (auto)

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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