rs146792467

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_013382.7(POMT2):c.439-45C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00437 in 1,552,670 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0032 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0045 ( 23 hom. )

Consequence

POMT2
NM_013382.7 intron

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.359

Publications

0 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 (BayesDel_noAF=-0.85).

BP6

Variant 14-77304845-G-A is Benign according to our data. Variant chr14-77304845-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 260301.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00321 (489/152370) while in subpopulation NFE AF = 0.00514 (350/68036). AF 95% confidence interval is 0.0047. There are 2 homozygotes in GnomAd4. There are 210 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

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.439-45C>T		intron	N/A	NP_037514.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
POMT2	ENST00000261534.9	TSL:1 MANE Select	c.439-45C>T	intron	N/A	ENSP00000261534.4	Q9UKY4-1
POMT2	ENST00000556326.5	TSL:1	n.*105-45C>T	intron	N/A	ENSP00000450630.1	Q9UKY4-2
POMT2	ENST00000682795.1		c.439-45C>T	intron	N/A	ENSP00000507574.1	A0A804HJN3

Frequencies

GnomAD3 genomes

AF:

0.00321

AC:

488

AN:

152252

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00104

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00190

Gnomad ASJ

AF:

0.0104

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00331

Gnomad FIN

AF:

0.000376

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00514

Gnomad OTH

AF:

0.00334

GnomAD2 exomes

AF:

0.00363

AC:

582

AN:

160402

AF XY:

0.00374

show subpopulations

Gnomad AFR exome

AF:

0.00107

Gnomad AMR exome

AF:

0.00246

Gnomad ASJ exome

AF:

0.0129

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000451

Gnomad NFE exome

AF:

0.00436

Gnomad OTH exome

AF:

0.00512

GnomAD4 exome

AF:

0.00449

AC:

6290

AN:

1400300

Hom.:

Cov.:

AF XY:

0.00448

AC XY:

3093

AN XY:

690946

show subpopulations

African (AFR)

AF:

0.000685

AC:

AN:

32100

American (AMR)

AF:

0.00249

AC:

AN:

35674

Ashkenazi Jewish (ASJ)

AF:

0.0113

AC:

285

AN:

25120

East Asian (EAS)

AF:

0.0000274

AC:

AN:

36448

South Asian (SAS)

AF:

0.00505

AC:

400

AN:

79230

European-Finnish (FIN)

AF:

0.000528

AC:

AN:

49276

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

5174

European-Non Finnish (NFE)

AF:

0.00473

AC:

5107

AN:

1079332

Other (OTH)

AF:

0.00530

AC:

307

AN:

57946

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

370

740

1110

1480

1850

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

194

388

582

776

970

<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:

0.00321

AC:

489

AN:

152370

Hom.:

Cov.:

AF XY:

0.00282

AC XY:

210

AN XY:

74518

show subpopulations

African (AFR)

AF:

0.00103

AC:

AN:

41588

American (AMR)

AF:

0.00189

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.0104

AC:

AN:

3470

East Asian (EAS)

AF:

0.000386

AC:

AN:

5188

South Asian (SAS)

AF:

0.00352

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.000376

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00514

AC:

350

AN:

68036

Other (OTH)

AF:

0.00331

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

100

125

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00490

Hom.:

Bravo

AF:

0.00323

Asia WGS

AF:

0.00202

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

2.1

(source)

DANN

Benign

0.38

PhyloP100

0.36

PromoterAI

-0.012

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over