rs2277152

Variant names:

• chr9-131520241-C-G
• rs2277152
• NM_001077365.2:c.1698+48C>G

Your query was ambiguous. Multiple possible variants found:

• chr9-131520241-C-G
• chr9-131520241-C-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001077365.2(POMT1):​c.1698+48C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.921 in 1,494,726 control chromosomes in the GnomAD database, including 637,871 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.85 (55948 hom., cov: 32)
  • Exomes 𝑓: 0.93 (581923 hom.)
• Consequence: POMT1 NM_001077365.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.168
• Publications: 13 publications found

Genes affected

POMT1 (HGNC:9202): (protein O-mannosyltransferase 1) The protein encoded by this gene is an O-mannosyltransferase that requires interaction with the product of the POMT2 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) and limb-girdle muscular dystrophy type 2K (LGMD2K). Several transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Oct 2008]

POMT1 Gene-Disease associations (from GenCC):

• muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A1

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Ambry Genetics, Laboratory for Molecular Medicine, Genomics England PanelApp
• myopathy caused by variation in POMT1

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B1

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• autosomal recessive limb-girdle muscular dystrophy type 2K

  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
• congenital muscular dystrophy without 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

ENSG00000230289 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 9-131520241-C-G is Benign according to our data. Variant chr9-131520241-C-G is described in ClinVar as Benign. ClinVar VariationId is 260142.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.94 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POMT1	NM_001077365.2	c.1698+48C>G		intron_variant	Intron 17 of 19	ENST00000402686.8	NP_001070833.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POMT1	ENST00000402686.8	c.1698+48C>G		intron_variant	Intron 17 of 19	1	NM_001077365.2	ENSP00000385797.4

Frequencies

GnomAD3 genomes AF: 0.848 AC: 128973 AN: 152094 Hom.: 55929 Cov.: 32

Gnomad AFR AF: 0.648

Gnomad AMI AF: 0.897

Gnomad AMR AF: 0.846

Gnomad ASJ AF: 0.922

Gnomad EAS AF: 0.917

Gnomad SAS AF: 0.962

Gnomad FIN AF: 0.935

Gnomad MID AF: 0.886

Gnomad NFE AF: 0.938

Gnomad OTH AF: 0.864

GnomAD2 exomes AF: 0.902 AC: 220470 AN: 244392 AF XY: 0.912

Gnomad AFR exome AF: 0.636

Gnomad AMR exome AF: 0.829

Gnomad ASJ exome AF: 0.925

Gnomad EAS exome AF: 0.915

Gnomad FIN exome AF: 0.931

Gnomad NFE exome AF: 0.936

Gnomad OTH exome AF: 0.913

GnomAD4 exome AF: 0.930 AC: 1247875 AN: 1342514 Hom.: 581923 Cov.: 19 AF XY: 0.932 AC XY: 628289 AN XY: 674356

African (AFR) AF: 0.636 AC: 19679 AN: 30966

American (AMR) AF: 0.830 AC: 36775 AN: 44290

Ashkenazi Jewish (ASJ) AF: 0.925 AC: 23507 AN: 25402

East Asian (EAS) AF: 0.916 AC: 35794 AN: 39056

South Asian (SAS) AF: 0.962 AC: 80515 AN: 83684

European-Finnish (FIN) AF: 0.930 AC: 47663 AN: 51224

Middle Eastern (MID) AF: 0.914 AC: 5080 AN: 5560

European-Non Finnish (NFE) AF: 0.942 AC: 947580 AN: 1005888

Other (OTH) AF: 0.909 AC: 51282 AN: 56444

GnomAD4 genome AF: 0.848 AC: 129027 AN: 152212 Hom.: 55948 Cov.: 32 AF XY: 0.850 AC XY: 63257 AN XY: 74424

African (AFR) AF: 0.648 AC: 26877 AN: 41502

American (AMR) AF: 0.846 AC: 12948 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.922 AC: 3200 AN: 3470

East Asian (EAS) AF: 0.917 AC: 4745 AN: 5174

South Asian (SAS) AF: 0.963 AC: 4647 AN: 4826

European-Finnish (FIN) AF: 0.935 AC: 9916 AN: 10608

Middle Eastern (MID) AF: 0.891 AC: 262 AN: 294

European-Non Finnish (NFE) AF: 0.938 AC: 63785 AN: 68016

Other (OTH) AF: 0.865 AC: 1829 AN: 2114

Alfa AF: 0.891 Hom.: 11237

Bravo AF: 0.829

Asia WGS AF: 0.890 AC: 3094 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jun 14, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: 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

- -

Autosomal recessive limb-girdle muscular dystrophy type 2K Benign:1

Oct 25, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B1 Benign:1

Oct 25, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A1 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	-0.85
CADD	Benign	2.2
DANN	Benign	0.45
PhyloP100		0.17
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2277152; hg19: chr9-134395628;