chr14-77276586-C-T

Variant names:

• chr14-77276586-C-T
• rs7159558
• NM_013382.7:c.*790G>A

Variant summary

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

The NM_013382.7(POMT2):​c.*790G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.556 in 152,182 control chromosomes in the GnomAD database, including 23,969 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.56 (23961 hom., cov: 33)
  • Exomes 𝑓: 0.44 (8 hom.)
• Consequence: POMT2 NM_013382.7 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.211
• Publications: 7 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 14-77276586-C-T is Benign according to our data. Variant chr14-77276586-C-T is described in ClinVar as Benign. ClinVar VariationId is 314536.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.595 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.*790G>A		3_prime_UTR	Exon 21 of 21	NP_037514.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POMT2	ENST00000261534.9	TSL:1 MANE Select	c.*790G>A		3_prime_UTR	Exon 21 of 21	ENSP00000261534.4	Q9UKY4-1
	POMT2	ENST00000905355.1		c.*790G>A		3_prime_UTR	Exon 22 of 22	ENSP00000575414.1
	POMT2	ENST00000682467.1		c.*790G>A		3_prime_UTR	Exon 20 of 20	ENSP00000508062.1	A0A804HKT3

Frequencies

GnomAD3 genomes AF: 0.556 AC: 84474 AN: 151980 Hom.: 23940 Cov.: 33

Gnomad AFR AF: 0.601

Gnomad AMI AF: 0.557

Gnomad AMR AF: 0.411

Gnomad ASJ AF: 0.504

Gnomad EAS AF: 0.444

Gnomad SAS AF: 0.453

Gnomad FIN AF: 0.638

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.567

Gnomad OTH AF: 0.533

GnomAD4 exome AF: 0.439 AC: 36 AN: 82 Hom.: 8 Cov.: 0 AF XY: 0.357 AC XY: 20 AN XY: 56

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.500 AC: 1 AN: 2

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.688 AC: 11 AN: 16

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.380 AC: 19 AN: 50

Other (OTH) AF: 0.625 AC: 5 AN: 8

GnomAD4 genome AF: 0.556 AC: 84528 AN: 152100 Hom.: 23961 Cov.: 33 AF XY: 0.554 AC XY: 41178 AN XY: 74380

African (AFR) AF: 0.601 AC: 24946 AN: 41500

American (AMR) AF: 0.410 AC: 6273 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.504 AC: 1749 AN: 3472

East Asian (EAS) AF: 0.445 AC: 2293 AN: 5156

South Asian (SAS) AF: 0.453 AC: 2183 AN: 4822

European-Finnish (FIN) AF: 0.638 AC: 6764 AN: 10594

Middle Eastern (MID) AF: 0.483 AC: 142 AN: 294

European-Non Finnish (NFE) AF: 0.567 AC: 38539 AN: 67954

Other (OTH) AF: 0.538 AC: 1137 AN: 2114

Alfa AF: 0.551 Hom.: 26406

Bravo AF: 0.540

Asia WGS AF: 0.486 AC: 1688 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Autosomal recessive limb-girdle muscular dystrophy type 2N (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.0
DANN	Benign	0.44
PhyloP100		0.21
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7159558; hg19: chr14-77742929;