14-77320520-C-T

Variant names:

• chr14-77320520-C-T
• rs2270420
• NM_013382.7:c.162G>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_013382.7(POMT2):​c.162G>A​(p.Ala54Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000713 in 1,401,542 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A54A) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: POMT2 NM_013382.7 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.256
• Publications: 0 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: G2P, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
• 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP7: Synonymous conserved (PhyloP=0.256 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POMT2	NM_013382.7	c.162G>A	p.Ala54Ala	synonymous_variant	Exon 1 of 21	ENST00000261534.9	NP_037514.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POMT2	ENST00000261534.9	c.162G>A	p.Ala54Ala	synonymous_variant	Exon 1 of 21	1	NM_013382.7	ENSP00000261534.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.14e-7 AC: 1 AN: 1401542 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 693288

African (AFR) AF: 0.00 AC: 0 AN: 32202

American (AMR) AF: 0.00 AC: 0 AN: 37992

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25314

East Asian (EAS) AF: 0.00 AC: 0 AN: 36542

South Asian (SAS) AF: 0.00 AC: 0 AN: 80690

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38382

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5706

European-Non Finnish (NFE) AF: 9.21e-7 AC: 1 AN: 1086284

Other (OTH) AF: 0.00 AC: 0 AN: 58430

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	6.8
DANN	Benign	0.81
PhyloP100		0.26
PromoterAI		-0.029	Neutral

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: rs2270420; hg19: chr14-77786863;