rs2302831

Variant names:

• chr14-77296129-T-C
• rs2302831
• NM_013382.7:c.1116+35A>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.1116+35A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0219 in 1,479,704 control chromosomes in the GnomAD database, including 507 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 (47 hom., cov: 31)
  • Exomes 𝑓: 0.022 (460 hom.)
• Consequence: POMT2 NM_013382.7 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.00900
• Publications: 3 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=-0.9).
• BP6: Variant 14-77296129-T-C is Benign according to our data. Variant chr14-77296129-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 260289.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0591 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.1116+35A>G		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.1116+35A>G		intron	N/A	ENSP00000261534.4	Q9UKY4-1
	POMT2	ENST00000682795.1		c.1116+35A>G		intron	N/A	ENSP00000507574.1	A0A804HJN3
	POMT2	ENST00000923942.1		c.1116+35A>G		intron	N/A	ENSP00000594001.1

Frequencies

GnomAD3 genomes AF: 0.0197 AC: 2997 AN: 152158 Hom.: 47 Cov.: 31

Gnomad AFR AF: 0.00463

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0342

Gnomad ASJ AF: 0.0596

Gnomad EAS AF: 0.0178

Gnomad SAS AF: 0.0470

Gnomad FIN AF: 0.0167

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0219

Gnomad OTH AF: 0.0325

GnomAD2 exomes AF: 0.0267 AC: 4685 AN: 175198 AF XY: 0.0280

Gnomad AFR exome AF: 0.00316

Gnomad AMR exome AF: 0.0334

Gnomad ASJ exome AF: 0.0557

Gnomad EAS exome AF: 0.0128

Gnomad FIN exome AF: 0.0174

Gnomad NFE exome AF: 0.0224

Gnomad OTH exome AF: 0.0358

GnomAD4 exome AF: 0.0221 AC: 29353 AN: 1327426 Hom.: 460 Cov.: 20 AF XY: 0.0233 AC XY: 15371 AN XY: 660650

African (AFR) AF: 0.00357 AC: 110 AN: 30848

American (AMR) AF: 0.0332 AC: 1225 AN: 36936

Ashkenazi Jewish (ASJ) AF: 0.0574 AC: 1422 AN: 24786

East Asian (EAS) AF: 0.0210 AC: 775 AN: 36876

South Asian (SAS) AF: 0.0473 AC: 3708 AN: 78434

European-Finnish (FIN) AF: 0.0172 AC: 848 AN: 49256

Middle Eastern (MID) AF: 0.0646 AC: 359 AN: 5558

European-Non Finnish (NFE) AF: 0.0193 AC: 19453 AN: 1009022

Other (OTH) AF: 0.0261 AC: 1453 AN: 55710

GnomAD4 genome AF: 0.0196 AC: 2992 AN: 152278 Hom.: 47 Cov.: 31 AF XY: 0.0205 AC XY: 1530 AN XY: 74466

African (AFR) AF: 0.00459 AC: 191 AN: 41570

American (AMR) AF: 0.0341 AC: 522 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0596 AC: 207 AN: 3472

East Asian (EAS) AF: 0.0176 AC: 91 AN: 5162

South Asian (SAS) AF: 0.0466 AC: 225 AN: 4824

European-Finnish (FIN) AF: 0.0167 AC: 177 AN: 10620

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0219 AC: 1489 AN: 68010

Other (OTH) AF: 0.0317 AC: 67 AN: 2112

Alfa AF: 0.0268 Hom.: 12

Bravo AF: 0.0187

Asia WGS AF: 0.0280 AC: 97 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.1
DANN	Benign	0.34
PhyloP100		0.0090
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs2302831; hg19: chr14-77762472;