chr14-77320520-C-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_013382.7(POMT2):c.162G>T(p.Ala54Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0673 in 1,553,826 control chromosomes in the GnomAD database, including 4,377 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. A54A) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.058 ( 390 hom., cov: 32)

Exomes 𝑓: 0.068 ( 3987 hom. )

Consequence

POMT2
NM_013382.7 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:12

Conservation

PhyloP100: 0.256

Publications

10 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.51).

BP6

Variant 14-77320520-C-A is Benign according to our data. Variant chr14-77320520-C-A is described in ClinVar as Benign. ClinVar VariationId is 95536.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.256 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.21 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.162G>T	p.Ala54Ala	synonymous	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.162G>T	p.Ala54Ala	synonymous	Exon 1 of 21	ENSP00000261534.4	Q9UKY4-1
POMT2	ENST00000556326.5	TSL:1	n.162G>T		non_coding_transcript_exon	Exon 1 of 6	ENSP00000450630.1	Q9UKY4-2
POMT2	ENST00000682795.1		c.162G>T	p.Ala54Ala	synonymous	Exon 1 of 22	ENSP00000507574.1	A0A804HJN3

Frequencies

GnomAD3 genomes

AF:

0.0579

AC:

8814

AN:

152188

Hom.:

391

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0117

Gnomad AMI

AF:

0.0636

Gnomad AMR

AF:

0.0453

Gnomad ASJ

AF:

0.0614

Gnomad EAS

AF:

0.221

Gnomad SAS

AF:

0.0746

Gnomad FIN

AF:

0.114

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.0657

Gnomad OTH

AF:

0.0760

GnomAD2 exomes

AF:

0.0744

AC:

11562

AN:

155460

AF XY:

0.0752

show subpopulations

Gnomad AFR exome

AF:

0.0106

Gnomad AMR exome

AF:

0.0326

Gnomad ASJ exome

AF:

0.0667

Gnomad EAS exome

AF:

0.242

Gnomad FIN exome

AF:

0.119

Gnomad NFE exome

AF:

0.0642

Gnomad OTH exome

AF:

0.0662

GnomAD4 exome

AF:

0.0684

AC:

95795

AN:

1401520

Hom.:

3987

Cov.:

AF XY:

0.0687

AC XY:

47624

AN XY:

693278

show subpopulations

African (AFR)

AF:

0.00922

AC:

297

AN:

32202

American (AMR)

AF:

0.0351

AC:

1335

AN:

37990

Ashkenazi Jewish (ASJ)

AF:

0.0647

AC:

1638

AN:

25314

East Asian (EAS)

AF:

0.223

AC:

8164

AN:

36540

South Asian (SAS)

AF:

0.0717

AC:

5788

AN:

80690

European-Finnish (FIN)

AF:

0.111

AC:

4276

AN:

38374

Middle Eastern (MID)

AF:

0.0494

AC:

282

AN:

5706

European-Non Finnish (NFE)

AF:

0.0642

AC:

69780

AN:

1086274

Other (OTH)

AF:

0.0725

AC:

4235

AN:

58430

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

6774

13547

20321

27094

33868

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2690

5380

8070

10760

13450

<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:

0.0578

AC:

8805

AN:

152306

Hom.:

390

Cov.:

AF XY:

0.0614

AC XY:

4576

AN XY:

74474

show subpopulations

African (AFR)

AF:

0.0117

AC:

485

AN:

41580

American (AMR)

AF:

0.0452

AC:

692

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.0614

AC:

213

AN:

3470

East Asian (EAS)

AF:

0.221

AC:

1142

AN:

5168

South Asian (SAS)

AF:

0.0741

AC:

358

AN:

4832

European-Finnish (FIN)

AF:

0.114

AC:

1211

AN:

10624

Middle Eastern (MID)

AF:

0.0680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0657

AC:

4467

AN:

68004

Other (OTH)

AF:

0.0752

AC:

159

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

415

829

1244

1658

2073

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome 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

Alfa

AF:

0.0640

Hom.:

483

Bravo

AF:

0.0527

Asia WGS

AF:

0.112

AC:

391

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (8)

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

BayesDel_noAF

Benign

-0.51

CADD

Benign

5.8

(source)

DANN

Benign

0.66

PhyloP100

0.26

PromoterAI

-0.019

Neutral

(source)

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over