rs79509556

Variant names:

• chr14-77296305-C-T
• rs79509556
• NM_013382.7:c.1007-32G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_013382.7(POMT2):​c.1007-32G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0291 in 1,483,100 control chromosomes in the GnomAD database, including 806 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.020 (37 hom., cov: 31)
  • Exomes 𝑓: 0.030 (769 hom.)
• Consequence: POMT2 NM_013382.7 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.0170
• Publications: 1 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 14-77296305-C-T is Benign according to our data. Variant chr14-77296305-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 260288.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.02 (3038/152264) while in subpopulation NFE AF = 0.0319 (2171/68016). AF 95% confidence interval is 0.0308. There are 37 homozygotes in GnomAd4. There are 1411 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 37 AR gene

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POMT2	NM_013382.7	MANE Select	c.1007-32G>A		intron	N/A	NP_037514.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POMT2	ENST00000261534.9	TSL:1 MANE Select	c.1007-32G>A		intron	N/A	ENSP00000261534.4
	POMT2	ENST00000682795.1		c.1007-32G>A		intron	N/A	ENSP00000507574.1
	POMT2	ENST00000682247.1		c.1007-32G>A		intron	N/A	ENSP00000507213.1

Frequencies

GnomAD3 genomes AF: 0.0200 AC: 3040 AN: 152146 Hom.: 37 Cov.: 31

Gnomad AFR AF: 0.00499

Gnomad AMI AF: 0.0373

Gnomad AMR AF: 0.0156

Gnomad ASJ AF: 0.0222

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.00538

Gnomad FIN AF: 0.0220

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0319

Gnomad OTH AF: 0.0229

GnomAD2 exomes AF: 0.0200 AC: 3525 AN: 175870 AF XY: 0.0202

Gnomad AFR exome AF: 0.00528

Gnomad AMR exome AF: 0.0124

Gnomad ASJ exome AF: 0.0201

Gnomad EAS exome AF: 0.0000751

Gnomad FIN exome AF: 0.0206

Gnomad NFE exome AF: 0.0324

Gnomad OTH exome AF: 0.0261

GnomAD4 exome AF: 0.0302 AC: 40165 AN: 1330836 Hom.: 769 Cov.: 20 AF XY: 0.0294 AC XY: 19510 AN XY: 662784

African (AFR) AF: 0.00453 AC: 140 AN: 30938

American (AMR) AF: 0.0134 AC: 504 AN: 37680

Ashkenazi Jewish (ASJ) AF: 0.0216 AC: 533 AN: 24732

East Asian (EAS) AF: 0.0000537 AC: 2 AN: 37242

South Asian (SAS) AF: 0.00656 AC: 519 AN: 79092

European-Finnish (FIN) AF: 0.0205 AC: 993 AN: 48522

Middle Eastern (MID) AF: 0.00479 AC: 26 AN: 5426

European-Non Finnish (NFE) AF: 0.0355 AC: 35879 AN: 1011298

Other (OTH) AF: 0.0281 AC: 1569 AN: 55906

GnomAD4 genome AF: 0.0200 AC: 3038 AN: 152264 Hom.: 37 Cov.: 31 AF XY: 0.0190 AC XY: 1411 AN XY: 74456

African (AFR) AF: 0.00498 AC: 207 AN: 41566

American (AMR) AF: 0.0156 AC: 239 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0222 AC: 77 AN: 3466

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5146

South Asian (SAS) AF: 0.00539 AC: 26 AN: 4826

European-Finnish (FIN) AF: 0.0220 AC: 234 AN: 10618

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0319 AC: 2171 AN: 68016

Other (OTH) AF: 0.0227 AC: 48 AN: 2116

Alfa AF: 0.0268 Hom.: 13

Bravo AF: 0.0193

Asia WGS AF: 0.00318 AC: 11 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	not specified (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.6
DANN	Benign	0.85
PhyloP100		0.017
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: rs79509556; hg19: chr14-77762648;