rs200163818

Variant names:

• chr14-77278484-C-A
• NM_013382.7:c.2057G>T

Your query was ambiguous. Multiple possible variants found:

• chr14-77278484-C-A
• chr14-77278484-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_013382.7(POMT2):​c.2057G>T​(p.Arg686Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000149 in 1,340,960 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R686Q) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: POMT2 NM_013382.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.16

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27873015).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POMT2	NM_013382.7	c.2057G>T	p.Arg686Leu	missense_variant	Exon 20 of 21	ENST00000261534.9	NP_037514.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POMT2	ENST00000261534.9	c.2057G>T	p.Arg686Leu	missense_variant	Exon 20 of 21	1	NM_013382.7	ENSP00000261534.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000149 AC: 2 AN: 1340960 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 664268

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000195

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Uncertain	0.046	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.52	D
Eigen	Benign	-0.12
Eigen_PC	Benign	0.039
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.056	D
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-0.62	T
MutationAssessor	Uncertain	2.3	M
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.99	N
REVEL	Uncertain	0.30
Sift	Benign	0.089	T
Sift4G	Benign	0.075	T
Polyphen		0.025	B
Vest4		0.41
MutPred		0.55		Gain of catalytic residue at W690 (P = 0);
MVP		0.78
MPC		0.10
ClinPred		0.90	D
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.17
gMVP		0.62

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-77744827;