NM_013382.7:c.1654-217A>G

Variant names:

• chr14-77280680-T-C
• rs2098380
• NM_013382.7:c.1654-217A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_013382.7(POMT2):​c.1654-217A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.333 in 148,644 control chromosomes in the GnomAD database, including 9,665 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.33 (9665 hom., cov: 33)
• Consequence: POMT2 NM_013382.7 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.81
• Publications: 4 publications found

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

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 14-77280680-T-C is Benign according to our data. Variant chr14-77280680-T-C is described in ClinVar as Benign. ClinVar VariationId is 668037.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.453 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.1654-217A>G		intron	N/A	NP_037514.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POMT2	ENST00000261534.9	TSL:1 MANE Select	c.1654-217A>G		intron	N/A	ENSP00000261534.4	Q9UKY4-1
	POMT2	ENST00000682795.1		c.1654-217A>G		intron	N/A	ENSP00000507574.1	A0A804HJN3
	POMT2	ENST00000923942.1		c.1654-217A>G		intron	N/A	ENSP00000594001.1

Frequencies

GnomAD3 genomes AF: 0.334 AC: 49535 AN: 148528 Hom.: 9654 Cov.: 33

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.410

Gnomad AMR AF: 0.421

Gnomad ASJ AF: 0.319

Gnomad EAS AF: 0.467

Gnomad SAS AF: 0.259

Gnomad FIN AF: 0.493

Gnomad MID AF: 0.261

Gnomad NFE AF: 0.410

Gnomad OTH AF: 0.343

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.333 AC: 49559 AN: 148644 Hom.: 9665 Cov.: 33 AF XY: 0.338 AC XY: 24486 AN XY: 72476

African (AFR) AF: 0.117 AC: 4582 AN: 39278

American (AMR) AF: 0.421 AC: 6339 AN: 15048

Ashkenazi Jewish (ASJ) AF: 0.319 AC: 1101 AN: 3450

East Asian (EAS) AF: 0.468 AC: 2362 AN: 5044

South Asian (SAS) AF: 0.258 AC: 1180 AN: 4572

European-Finnish (FIN) AF: 0.493 AC: 5131 AN: 10414

Middle Eastern (MID) AF: 0.245 AC: 70 AN: 286

European-Non Finnish (NFE) AF: 0.410 AC: 27704 AN: 67592

Other (OTH) AF: 0.350 AC: 721 AN: 2060

Alfa AF: 0.379 Hom.: 20761

Bravo AF: 0.317

Asia WGS AF: 0.345 AC: 1196 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.19
DANN	Benign	0.61
PhyloP100		-1.8
PromoterAI		0.0029	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2098380; hg19: chr14-77747023;