chr14-77320032-G-A

Variant names:

• chr14-77320032-G-A
• rs7160195
• NM_013382.7:c.248+402C>T

Variant summary

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

The NM_013382.7(POMT2):​c.248+402C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.327 in 152,014 control chromosomes in the GnomAD database, including 8,306 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 0.33 (8306 hom., cov: 32)
• Consequence: POMT2 NM_013382.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0230
• Publications: 9 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.428 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POMT2	NM_013382.7	c.248+402C>T		intron_variant	Intron 1 of 20	ENST00000261534.9	NP_037514.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POMT2	ENST00000261534.9	c.248+402C>T		intron_variant	Intron 1 of 20	1	NM_013382.7	ENSP00000261534.4

Frequencies

GnomAD3 genomes AF: 0.327 AC: 49678 AN: 151896 Hom.: 8288 Cov.: 32

Gnomad AFR AF: 0.346

Gnomad AMI AF: 0.299

Gnomad AMR AF: 0.258

Gnomad ASJ AF: 0.290

Gnomad EAS AF: 0.442

Gnomad SAS AF: 0.197

Gnomad FIN AF: 0.386

Gnomad MID AF: 0.277

Gnomad NFE AF: 0.326

Gnomad OTH AF: 0.307

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

GnomAD4 genome AF: 0.327 AC: 49721 AN: 152014 Hom.: 8306 Cov.: 32 AF XY: 0.325 AC XY: 24165 AN XY: 74294

African (AFR) AF: 0.346 AC: 14348 AN: 41432

American (AMR) AF: 0.258 AC: 3939 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.290 AC: 1004 AN: 3468

East Asian (EAS) AF: 0.443 AC: 2283 AN: 5150

South Asian (SAS) AF: 0.195 AC: 940 AN: 4824

European-Finnish (FIN) AF: 0.386 AC: 4081 AN: 10568

Middle Eastern (MID) AF: 0.274 AC: 80 AN: 292

European-Non Finnish (NFE) AF: 0.326 AC: 22124 AN: 67968

Other (OTH) AF: 0.307 AC: 649 AN: 2116

Alfa AF: 0.342 Hom.: 1297

Bravo AF: 0.321

Asia WGS AF: 0.295 AC: 1022 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.8
DANN	Benign	0.54
PhyloP100		-0.023
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: rs7160195; hg19: chr14-77786375;