NM_013382.7:c.*2325A>G

Variant names:

• chr14-77275051-T-C
• rs11547793
• NM_013382.7:c.*2325A>G

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.*2325A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.228 in 152,160 control chromosomes in the GnomAD database, including 4,346 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.23 (4346 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: POMT2 NM_013382.7 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.28
• 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: G2P, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
• 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=-0.76).
• BP6: Variant 14-77275051-T-C is Benign according to our data. Variant chr14-77275051-T-C is described in ClinVar as Benign. ClinVar VariationId is 314507.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.471 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.*2325A>G		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.*2325A>G		3_prime_UTR	Exon 21 of 21	ENSP00000261534.4	Q9UKY4-1
	POMT2	ENST00000905355.1		c.*2325A>G		3_prime_UTR	Exon 22 of 22	ENSP00000575414.1
	POMT2	ENST00000682467.1		c.*2325A>G		3_prime_UTR	Exon 20 of 20	ENSP00000508062.1	A0A804HKT3

Frequencies

GnomAD3 genomes AF: 0.228 AC: 34694 AN: 152040 Hom.: 4337 Cov.: 32

Gnomad AFR AF: 0.173

Gnomad AMI AF: 0.289

Gnomad AMR AF: 0.309

Gnomad ASJ AF: 0.293

Gnomad EAS AF: 0.487

Gnomad SAS AF: 0.283

Gnomad FIN AF: 0.198

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.220

Gnomad OTH AF: 0.252

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.228 AC: 34724 AN: 152160 Hom.: 4346 Cov.: 32 AF XY: 0.232 AC XY: 17235 AN XY: 74382

African (AFR) AF: 0.173 AC: 7183 AN: 41522

American (AMR) AF: 0.310 AC: 4731 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.293 AC: 1016 AN: 3466

East Asian (EAS) AF: 0.486 AC: 2516 AN: 5172

South Asian (SAS) AF: 0.283 AC: 1363 AN: 4812

European-Finnish (FIN) AF: 0.198 AC: 2096 AN: 10596

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.220 AC: 14967 AN: 67994

Other (OTH) AF: 0.250 AC: 530 AN: 2116

Alfa AF: 0.231 Hom.: 5573

Bravo AF: 0.238

Asia WGS AF: 0.357 AC: 1242 AN: 3478

ClinVar

ClinVar submissions as Germline

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	-0.76
CADD	Benign	9.8
DANN	Benign	0.76
PhyloP100		1.3
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: rs11547793; hg19: chr14-77741394;