14-77278850-A-C

Variant names:

• chr14-77278850-A-C
• rs3209079
• NM_013382.7:c.1911T>G

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_013382.7(POMT2):​c.1911T>G​(p.Leu637Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.807 in 1,613,018 control chromosomes in the GnomAD database, including 526,421 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.82 (51439 hom., cov: 33)
  • Exomes 𝑓: 0.81 (474982 hom.)
• Consequence: POMT2 NM_013382.7 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: -0.748
• Publications: 21 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.091).
• BP6: Variant 14-77278850-A-C is Benign according to our data. Variant chr14-77278850-A-C is described in ClinVar as Benign. ClinVar VariationId is 166901.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.748 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.929 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.1911T>G	p.Leu637Leu	synonymous	Exon 19 of 21	NP_037514.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POMT2	ENST00000261534.9	TSL:1 MANE Select	c.1911T>G	p.Leu637Leu	synonymous	Exon 19 of 21	ENSP00000261534.4	Q9UKY4-1
	POMT2	ENST00000682247.1		c.1900T>G	p.Ser634Ala	missense	Exon 19 of 21	ENSP00000507213.1	A0A804HIT3
	POMT2	ENST00000682795.1		c.2058T>G	p.Leu686Leu	synonymous	Exon 20 of 22	ENSP00000507574.1	A0A804HJN3

Frequencies

GnomAD3 genomes AF: 0.821 AC: 124889 AN: 152092 Hom.: 51399 Cov.: 33

Gnomad AFR AF: 0.838

Gnomad AMI AF: 0.849

Gnomad AMR AF: 0.761

Gnomad ASJ AF: 0.831

Gnomad EAS AF: 0.951

Gnomad SAS AF: 0.785

Gnomad FIN AF: 0.857

Gnomad MID AF: 0.753

Gnomad NFE AF: 0.811

Gnomad OTH AF: 0.833

GnomAD2 exomes AF: 0.815 AC: 203865 AN: 250248 AF XY: 0.814

Gnomad AFR exome AF: 0.842

Gnomad AMR exome AF: 0.737

Gnomad ASJ exome AF: 0.819

Gnomad EAS exome AF: 0.964

Gnomad FIN exome AF: 0.847

Gnomad NFE exome AF: 0.814

Gnomad OTH exome AF: 0.814

GnomAD4 exome AF: 0.805 AC: 1176648 AN: 1460808 Hom.: 474982 Cov.: 72 AF XY: 0.805 AC XY: 584837 AN XY: 726742

African (AFR) AF: 0.844 AC: 28235 AN: 33460

American (AMR) AF: 0.747 AC: 33376 AN: 44690

Ashkenazi Jewish (ASJ) AF: 0.823 AC: 21511 AN: 26132

East Asian (EAS) AF: 0.967 AC: 38376 AN: 39698

South Asian (SAS) AF: 0.772 AC: 66545 AN: 86244

European-Finnish (FIN) AF: 0.845 AC: 44635 AN: 52850

Middle Eastern (MID) AF: 0.796 AC: 4590 AN: 5764

European-Non Finnish (NFE) AF: 0.801 AC: 890377 AN: 1111610

Other (OTH) AF: 0.812 AC: 49003 AN: 60360

GnomAD4 genome AF: 0.821 AC: 124983 AN: 152210 Hom.: 51439 Cov.: 33 AF XY: 0.823 AC XY: 61244 AN XY: 74428

African (AFR) AF: 0.838 AC: 34798 AN: 41530

American (AMR) AF: 0.760 AC: 11625 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.831 AC: 2885 AN: 3472

East Asian (EAS) AF: 0.951 AC: 4918 AN: 5170

South Asian (SAS) AF: 0.785 AC: 3788 AN: 4828

European-Finnish (FIN) AF: 0.857 AC: 9091 AN: 10612

Middle Eastern (MID) AF: 0.752 AC: 221 AN: 294

European-Non Finnish (NFE) AF: 0.811 AC: 55114 AN: 67984

Other (OTH) AF: 0.836 AC: 1769 AN: 2116

Alfa AF: 0.812 Hom.: 42595

Bravo AF: 0.816

Asia WGS AF: 0.874 AC: 3042 AN: 3478

EpiCase AF: 0.809

EpiControl AF: 0.811

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	not specified (5)
-	-	1	Autosomal recessive limb-girdle muscular dystrophy type 2N (1)
-	-	1	Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A2 (1)
-	-	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	Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B2 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.7
DANN	Benign	0.55
PhyloP100		-0.75
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
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: rs3209079; hg19: chr14-77745193; COSMIC: COSV55071450; COSMIC: COSV55071450;