14-77320521-G-T

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.161C>A(p.Ala54Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00549 in 1,554,514 control chromosomes in the GnomAD database, including 445 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A54T) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.029 ( 219 hom., cov: 32)

Exomes 𝑓: 0.0030 ( 226 hom. )

Consequence

POMT2
NM_013382.7 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -0.106

Publications

7 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: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), G2P
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 (MetaRNN=0.0016682744).

BP6

Variant 14-77320521-G-T is Benign according to our data. Variant chr14-77320521-G-T is described in ClinVar as Benign. ClinVar VariationId is 130016.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0975 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013382.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POMT2	NM_013382.7	MANE Select	c.161C>A	p.Ala54Glu	missense	Exon 1 of 21	NP_037514.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
POMT2	ENST00000261534.9	TSL:1 MANE Select	c.161C>A	p.Ala54Glu	missense	Exon 1 of 21	ENSP00000261534.4	Q9UKY4-1
POMT2	ENST00000556326.5	TSL:1	n.161C>A		non_coding_transcript_exon	Exon 1 of 6	ENSP00000450630.1	Q9UKY4-2
POMT2	ENST00000682795.1		c.161C>A	p.Ala54Glu	missense	Exon 1 of 22	ENSP00000507574.1	A0A804HJN3

Frequencies

GnomAD3 genomes

AF:

0.0286

AC:

4350

AN:

152150

Hom.:

219

Cov.:

show subpopulations

Gnomad AFR

AF:

0.100

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00837

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000827

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000323

Gnomad OTH

AF:

0.0210

GnomAD2 exomes

AF:

0.00678

AC:

1060

AN:

156336

AF XY:

0.00480

show subpopulations

Gnomad AFR exome

AF:

0.106

Gnomad AMR exome

AF:

0.00322

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000223

Gnomad OTH exome

AF:

0.00335

GnomAD4 exome

AF:

0.00298

AC:

4173

AN:

1402246

Hom.:

226

Cov.:

AF XY:

0.00254

AC XY:

1765

AN XY:

693734

show subpopulations

African (AFR)

AF:

0.109

AC:

3524

AN:

32210

American (AMR)

AF:

0.00449

AC:

171

AN:

38082

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25316

East Asian (EAS)

AF:

0.00

AC:

AN:

36630

South Asian (SAS)

AF:

0.000136

AC:

AN:

80770

European-Finnish (FIN)

AF:

0.00

AC:

AN:

38246

Middle Eastern (MID)

AF:

0.00228

AC:

AN:

5708

European-Non Finnish (NFE)

AF:

0.0000994

AC:

108

AN:

1086810

Other (OTH)

AF:

0.00592

AC:

346

AN:

58474

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

270

541

811

1082

1352

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

114

228

342

456

570

<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:

0.0286

AC:

4355

AN:

152268

Hom.:

219

Cov.:

AF XY:

0.0272

AC XY:

2026

AN XY:

74466

show subpopulations

African (AFR)

AF:

0.100

AC:

4158

AN:

41554

American (AMR)

AF:

0.00836

AC:

128

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5166

South Asian (SAS)

AF:

0.000621

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000324

AC:

AN:

68000

Other (OTH)

AF:

0.0208

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

193

385

578

770

963

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

160

200

<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:

0.00472

Hom.:

Bravo

AF:

0.0327

ESP6500AA

AF:

0.0878

AC:

359

ESP6500EA

AF:

0.000364

AC:

ExAC

AF:

0.00636

AC:

725

Asia WGS

AF:

0.00549

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (5)

not provided (2)

Autosomal recessive limb-girdle muscular dystrophy type 2N (1)

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 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.50

CADD

Benign

2.2

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.054

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.077

LIST_S2

Benign

0.50

MetaRNN

Benign

0.0017

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.63

PhyloP100

-0.11

PrimateAI

Uncertain

0.58

PROVEAN

Benign

0.99

REVEL

Benign

0.098

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0010

Vest4

0.16

MVP

0.47

MPC

0.096

ClinPred

0.0082

GERP RS

-1.7

PromoterAI

0.026

Neutral

(source)

Varity_R

0.048

gMVP

0.55

Mutation Taster

=97/3

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over