rs4899650

Variant names:

• chr14-77310158-T-A
• rs4899650
• NM_013382.7:c.333+1791A>T

Your query was ambiguous. Multiple possible variants found:

• chr14-77310158-T-A
• chr14-77310158-T-C
• chr14-77310158-T-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_013382.7(POMT2):​c.333+1791A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.381 in 152,064 control chromosomes in the GnomAD database, including 11,171 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.38 (11171 hom., cov: 32)
• Consequence: POMT2 NM_013382.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.38
• Publications: 5 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, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.45 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.333+1791A>T		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.333+1791A>T		intron	N/A	ENSP00000261534.4
	POMT2	ENST00000556326.5	TSL:1	n.249-3717A>T		intron	N/A	ENSP00000450630.1
	POMT2	ENST00000682795.1		c.333+1791A>T		intron	N/A	ENSP00000507574.1

Frequencies

GnomAD3 genomes AF: 0.380 AC: 57812 AN: 151946 Hom.: 11146 Cov.: 32

Gnomad AFR AF: 0.359

Gnomad AMI AF: 0.368

Gnomad AMR AF: 0.313

Gnomad ASJ AF: 0.367

Gnomad EAS AF: 0.464

Gnomad SAS AF: 0.276

Gnomad FIN AF: 0.446

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.401

Gnomad OTH AF: 0.364

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

GnomAD4 genome AF: 0.381 AC: 57866 AN: 152064 Hom.: 11171 Cov.: 32 AF XY: 0.379 AC XY: 28174 AN XY: 74346

African (AFR) AF: 0.360 AC: 14914 AN: 41458

American (AMR) AF: 0.313 AC: 4783 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.367 AC: 1274 AN: 3468

East Asian (EAS) AF: 0.465 AC: 2402 AN: 5164

South Asian (SAS) AF: 0.275 AC: 1326 AN: 4826

European-Finnish (FIN) AF: 0.446 AC: 4713 AN: 10564

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.401 AC: 27242 AN: 67972

Other (OTH) AF: 0.370 AC: 782 AN: 2112

Alfa AF: 0.286 Hom.: 763

Bravo AF: 0.371

Asia WGS AF: 0.368 AC: 1277 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.077
DANN	Benign	0.43
PhyloP100		-1.4
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: rs4899650; hg19: chr14-77776501;