14-77291400-G-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PP3_Moderate

The NM_013382.7(POMT2):​c.1117-20C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.0 (0 hom., cov: 21)
  • Exomes 𝑓: 0.0000022 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: POMT2 NM_013382.7 intron
• Clinical Significance: Not reported in ClinVar
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

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>A		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>A		intron	N/A	ENSP00000261534.4	Q9UKY4-1
	POMT2	ENST00000682795.1		c.1117-20C>A		intron	N/A	ENSP00000507574.1	A0A804HJN3
	POMT2	ENST00000923942.1		c.1117-20C>A		intron	N/A	ENSP00000594001.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 116026 Hom.: 0 Cov.: 21

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000216 AC: 1 AN: 462856 Hom.: 0 Cov.: 9 AF XY: 0.00 AC XY: 0 AN XY: 245916

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 18068

American (AMR) AF: 0.00 AC: 0 AN: 24512

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11756

East Asian (EAS) AF: 0.00 AC: 0 AN: 13166

South Asian (SAS) AF: 0.00 AC: 0 AN: 63096

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 28598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1778

European-Non Finnish (NFE) AF: 0.00000355 AC: 1 AN: 281782

Other (OTH) AF: 0.00 AC: 0 AN: 20100

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 116026 Hom.: 0 Cov.: 21 AF XY: 0.00 AC XY: 0 AN XY: 53346

African (AFR) AF: 0.00 AC: 0 AN: 31696

American (AMR) AF: 0.00 AC: 0 AN: 8860

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3106

East Asian (EAS) AF: 0.00 AC: 0 AN: 3102

South Asian (SAS) AF: 0.00 AC: 0 AN: 2986

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5144

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 156

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 58658

Other (OTH) AF: 0.00 AC: 0 AN: 1524

Alfa AF: 0.00 Hom.: 118

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.11
DANN	Benign	0.26
PhyloP100		-1.2

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.93		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.93		Position offset: -2
DS_AL_spliceai		0.88		Position offset: -20

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7153929; hg19: chr14-77757743;