Variant 11-74342575-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4BS1_Supporting

The NM_173582.6(PGM2L1):c.1518G>T(p.Arg506Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000504 in 1,605,678 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. Variant has been reported in ClinVar as Uncertain significance (★). Another nucleotide change resulting in same amino acid change has been previously reported as Uncertain significancein ClinVar.

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000047 ( 0 hom. )

Consequence

PGM2L1
NM_173582.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.22

Variant links:

Genes affected

PGM2L1 (HGNC:20898): (phosphoglucomutase 2 like 1) Enables glucose-1,6-bisphosphate synthase activity. Predicted to be involved in glucose metabolic process and phosphorylation. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

PGM2L1 links:

LOC112268078 (HGNC:):

LOC112268078 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3371818).

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0000789 (12/152076) while in subpopulation NFE AF= 0.000162 (11/68024). AF 95% confidence interval is 0.0000905. There are 0 homozygotes in gnomad4. There are 7 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
PGM2L1	NM_173582.6 linkuse as main transcript	c.1518G>T	p.Arg506Ser	missense_variant	12/14	ENST00000298198.5
LOC112268078	XR_002957258.2 linkuse as main transcript	n.314+13087C>A		intron_variant, non_coding_transcript_variant
PGM2L1	XM_011544953.4 linkuse as main transcript	c.1581G>T	p.Arg527Ser	missense_variant	13/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PGM2L1	ENST00000298198.5 linkuse as main transcript	c.1518G>T	p.Arg506Ser	missense_variant	12/14	1	NM_173582.6	P1

Frequencies

GnomAD3 genomes

AF:

0.0000789

AC:

AN:

152076

Hom.:

Cov.:

show subpopulations

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:

0.0000945

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000404

AC:

AN:

247236

Hom.:

AF XY:

0.0000299

AC XY:

AN XY:

133688

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000340

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000800

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000475

AC:

AN:

1453602

Hom.:

Cov.:

AF XY:

0.0000470

AC XY:

AN XY:

723060

show subpopulations

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:

0.0000354

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000596

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000789

AC:

AN:

152076

Hom.:

Cov.:

AF XY:

0.0000942

AC XY:

AN XY:

74276

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000945

Gnomad4 NFE

AF:

0.000162

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000229

Hom.:

Bravo

AF:

0.0000907

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000412

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 08, 2021

The c.1518G>T (p.R506S) alteration is located in exon 12 (coding exon 12) of the PGM2L1 gene. This alteration results from a G to T substitution at nucleotide position 1518, causing the arginine (R) at amino acid position 506 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.31

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.25

Eigen

Benign

-0.59

Eigen_PC

Benign

-0.57

FATHMM_MKL

Benign

0.19

LIST_S2

Uncertain

0.88

M_CAP

Benign

0.011

MetaRNN

Benign

0.34

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.5

MutationTaster

Benign

1.0

PrimateAI

Benign

0.43

PROVEAN

Pathogenic

-5.0

REVEL

Benign

0.27

Sift

Uncertain

0.027

Sift4G

Uncertain

0.041

Polyphen

0.0030

Vest4

0.63

MutPred

0.52

Loss of helix (P = 0.028);

MVP

0.33

MPC

0.71

ClinPred

0.53

GERP RS

-1.5

Varity_R

0.48

gMVP

0.70

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over