14-77306486-A-G

Variant names:

• chr14-77306486-A-G
• rs66502123
• NM_013382.7:c.334-45T>C

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.334-45T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 1,602,448 control chromosomes in the GnomAD database, including 11,093 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.087 (735 hom., cov: 32)
  • Exomes 𝑓: 0.11 (10358 hom.)
• Consequence: POMT2 NM_013382.7 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.561
• Publications: 5 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=-0.71).
• BP6: Variant 14-77306486-A-G is Benign according to our data. Variant chr14-77306486-A-G is described in ClinVar as Benign. ClinVar VariationId is 260300.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.179 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.334-45T>C		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.334-45T>C		intron	N/A	ENSP00000261534.4	Q9UKY4-1
	POMT2	ENST00000556326.5	TSL:1	n.249-45T>C		intron	N/A	ENSP00000450630.1	Q9UKY4-2
	POMT2	ENST00000682795.1		c.334-45T>C		intron	N/A	ENSP00000507574.1	A0A804HJN3

Frequencies

GnomAD3 genomes AF: 0.0875 AC: 13310 AN: 152158 Hom.: 735 Cov.: 32

Gnomad AFR AF: 0.0334

Gnomad AMI AF: 0.121

Gnomad AMR AF: 0.0661

Gnomad ASJ AF: 0.124

Gnomad EAS AF: 0.00848

Gnomad SAS AF: 0.188

Gnomad FIN AF: 0.0955

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.120

Gnomad OTH AF: 0.0865

GnomAD2 exomes AF: 0.104 AC: 25729 AN: 246266 AF XY: 0.113

Gnomad AFR exome AF: 0.0304

Gnomad AMR exome AF: 0.0471

Gnomad ASJ exome AF: 0.129

Gnomad EAS exome AF: 0.00539

Gnomad FIN exome AF: 0.101

Gnomad NFE exome AF: 0.123

Gnomad OTH exome AF: 0.102

GnomAD4 exome AF: 0.113 AC: 164574 AN: 1450172 Hom.: 10358 Cov.: 29 AF XY: 0.117 AC XY: 84298 AN XY: 721308

African (AFR) AF: 0.0274 AC: 910 AN: 33246

American (AMR) AF: 0.0489 AC: 2166 AN: 44280

Ashkenazi Jewish (ASJ) AF: 0.131 AC: 3378 AN: 25816

East Asian (EAS) AF: 0.00466 AC: 184 AN: 39466

South Asian (SAS) AF: 0.192 AC: 16470 AN: 85816

European-Finnish (FIN) AF: 0.0988 AC: 5229 AN: 52926

Middle Eastern (MID) AF: 0.144 AC: 822 AN: 5708

European-Non Finnish (NFE) AF: 0.117 AC: 128679 AN: 1103072

Other (OTH) AF: 0.113 AC: 6736 AN: 59842

GnomAD4 genome AF: 0.0874 AC: 13312 AN: 152276 Hom.: 735 Cov.: 32 AF XY: 0.0886 AC XY: 6593 AN XY: 74452

African (AFR) AF: 0.0334 AC: 1389 AN: 41576

American (AMR) AF: 0.0658 AC: 1006 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.124 AC: 431 AN: 3472

East Asian (EAS) AF: 0.00850 AC: 44 AN: 5178

South Asian (SAS) AF: 0.189 AC: 910 AN: 4818

European-Finnish (FIN) AF: 0.0955 AC: 1013 AN: 10608

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.120 AC: 8184 AN: 68016

Other (OTH) AF: 0.0856 AC: 181 AN: 2114

Alfa AF: 0.105 Hom.: 215

Bravo AF: 0.0784

Asia WGS AF: 0.117 AC: 411 AN: 3478

ClinVar

ClinVar submissions

Significance: 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	-0.71
CADD	Benign	14
DANN	Benign	0.86
PhyloP100		0.56
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs66502123; hg19: chr14-77772829;