rs2302831

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_013382.7(POMT2):c.1116+35A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0219 in 1,479,704 control chromosomes in the GnomAD database, including 507 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.020 ( 47 hom., cov: 31)

Exomes 𝑓: 0.022 ( 460 hom. )

Consequence

POMT2
NM_013382.7 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.00900

Publications

3 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 14-77296129-T-C is Benign according to our data. Variant chr14-77296129-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 260289.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0591 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POMT2	NM_013382.7 link	c.1116+35A>G		intron_variant	Intron 9 of 20	ENST00000261534.9	NP_037514.2	Q9UKY4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POMT2	ENST00000261534.9 link	c.1116+35A>G		intron_variant	Intron 9 of 20	1	NM_013382.7	ENSP00000261534.4		Q9UKY4-1

Frequencies

GnomAD3 genomes

AF:

0.0197

AC:

2997

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00463

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.0342

Gnomad ASJ

AF:

0.0596

Gnomad EAS

AF:

0.0178

Gnomad SAS

AF:

0.0470

Gnomad FIN

AF:

0.0167

Gnomad MID

AF:

0.0665

Gnomad NFE

AF:

0.0219

Gnomad OTH

AF:

0.0325

GnomAD2 exomes

AF:

0.0267

AC:

4685

AN:

175198

AF XY:

0.0280

show subpopulations

Gnomad AFR exome

AF:

0.00316

Gnomad AMR exome

AF:

0.0334

Gnomad ASJ exome

AF:

0.0557

Gnomad EAS exome

AF:

0.0128

Gnomad FIN exome

AF:

0.0174

Gnomad NFE exome

AF:

0.0224

Gnomad OTH exome

AF:

0.0358

GnomAD4 exome

AF:

0.0221

AC:

29353

AN:

1327426

Hom.:

460

Cov.:

AF XY:

0.0233

AC XY:

15371

AN XY:

660650

show subpopulations

African (AFR)

AF:

0.00357

AC:

110

AN:

30848

American (AMR)

AF:

0.0332

AC:

1225

AN:

36936

Ashkenazi Jewish (ASJ)

AF:

0.0574

AC:

1422

AN:

24786

East Asian (EAS)

AF:

0.0210

AC:

775

AN:

36876

South Asian (SAS)

AF:

0.0473

AC:

3708

AN:

78434

European-Finnish (FIN)

AF:

0.0172

AC:

848

AN:

49256

Middle Eastern (MID)

AF:

0.0646

AC:

359

AN:

5558

European-Non Finnish (NFE)

AF:

0.0193

AC:

19453

AN:

1009022

Other (OTH)

AF:

0.0261

AC:

1453

AN:

55710

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

Heterozygous variant carriers

1692

3383

5075

6766

8458

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

716

1432

2148

2864

3580

<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:

0.0196

AC:

2992

AN:

152278

Hom.:

Cov.:

AF XY:

0.0205

AC XY:

1530

AN XY:

74466

show subpopulations

African (AFR)

AF:

0.00459

AC:

191

AN:

41570

American (AMR)

AF:

0.0341

AC:

522

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0596

AC:

207

AN:

3472

East Asian (EAS)

AF:

0.0176

AC:

AN:

5162

South Asian (SAS)

AF:

0.0466

AC:

225

AN:

4824

European-Finnish (FIN)

AF:

0.0167

AC:

177

AN:

10620

Middle Eastern (MID)

AF:

0.0714

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0219

AC:

1489

AN:

68010

Other (OTH)

AF:

0.0317

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

155

311

466

622

777

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

102

136

170

<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:

0.0268

Hom.:

Bravo

AF:

0.0187

Asia WGS

AF:

0.0280

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jul 15, 2018

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

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

-0.90

CADD

Benign

1.1

(source)

DANN

Benign

0.34

PhyloP100

0.0090

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

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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