rs7153929

Variant names:

• chr14-77291400-G-A
• rs7153929
• NM_013382.7:c.1117-20C>T

Your query was ambiguous. Multiple possible variants found:

• chr14-77291400-G-A
• chr14-77291400-G-T

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.1117-20C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 578,046 control chromosomes in the GnomAD database, including 3,351 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (1264 hom., cov: 21)
  • Exomes 𝑓: 0.11 (2087 hom.)
• Consequence: POMT2 NM_013382.7 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -1.21
• Publications: 2 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=-0.92).
• BP6: Variant 14-77291400-G-A is Benign according to our data. Variant chr14-77291400-G-A is described in ClinVar as Benign. ClinVar VariationId is 95533.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.277 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.1117-20C>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.1117-20C>T		intron	N/A	ENSP00000261534.4	Q9UKY4-1
	POMT2	ENST00000682795.1		c.1117-20C>T		intron	N/A	ENSP00000507574.1	A0A804HJN3
	POMT2	ENST00000923942.1		c.1117-20C>T		intron	N/A	ENSP00000594001.1

Frequencies

GnomAD3 genomes AF: 0.113 AC: 13059 AN: 115916 Hom.: 1264 Cov.: 21

Gnomad AFR AF: 0.282

Gnomad AMI AF: 0.0718

Gnomad AMR AF: 0.0733

Gnomad ASJ AF: 0.0605

Gnomad EAS AF: 0.000322

Gnomad SAS AF: 0.0687

Gnomad FIN AF: 0.0869

Gnomad MID AF: 0.122

Gnomad NFE AF: 0.0411

Gnomad OTH AF: 0.111

GnomAD2 exomes AF: 0.0648 AC: 11401 AN: 175986 AF XY: 0.0614

Gnomad AFR exome AF: 0.313

Gnomad AMR exome AF: 0.0385

Gnomad ASJ exome AF: 0.0583

Gnomad EAS exome AF: 0.000439

Gnomad FIN exome AF: 0.0611

Gnomad NFE exome AF: 0.0477

Gnomad OTH exome AF: 0.0580

GnomAD4 exome AF: 0.115 AC: 53027 AN: 462044 Hom.: 2087 Cov.: 9 AF XY: 0.109 AC XY: 26728 AN XY: 245522

African (AFR) AF: 0.406 AC: 7312 AN: 17996

American (AMR) AF: 0.0484 AC: 1187 AN: 24508

Ashkenazi Jewish (ASJ) AF: 0.0994 AC: 1168 AN: 11756

East Asian (EAS) AF: 0.000608 AC: 8 AN: 13168

South Asian (SAS) AF: 0.0667 AC: 4208 AN: 63066

European-Finnish (FIN) AF: 0.0807 AC: 2306 AN: 28580

Middle Eastern (MID) AF: 0.115 AC: 204 AN: 1776

European-Non Finnish (NFE) AF: 0.121 AC: 34030 AN: 281142

Other (OTH) AF: 0.130 AC: 2604 AN: 20052

GnomAD4 genome AF: 0.113 AC: 13078 AN: 116002 Hom.: 1264 Cov.: 21 AF XY: 0.115 AC XY: 6145 AN XY: 53358

African (AFR) AF: 0.282 AC: 8935 AN: 31692

American (AMR) AF: 0.0732 AC: 648 AN: 8856

Ashkenazi Jewish (ASJ) AF: 0.0605 AC: 188 AN: 3106

East Asian (EAS) AF: 0.000322 AC: 1 AN: 3104

South Asian (SAS) AF: 0.0690 AC: 206 AN: 2984

European-Finnish (FIN) AF: 0.0869 AC: 447 AN: 5142

Middle Eastern (MID) AF: 0.120 AC: 18 AN: 150

European-Non Finnish (NFE) AF: 0.0411 AC: 2410 AN: 58640

Other (OTH) AF: 0.110 AC: 168 AN: 1534

Alfa AF: 0.0650 Hom.: 118

Bravo AF: 0.106

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	6	not specified (6)
-	-	1	Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A2;C3150416:Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B2;C3150418: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	-0.92
CADD	Benign	0.43
DANN	Benign	0.25
PhyloP100		-1.2
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: rs7153929; hg19: chr14-77757743;