Variant 11-74342528-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_173582.6(PGM2L1):c.1565C>T(p.Thr522Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00237 in 1,609,584 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0025 ( 3 hom. )

Consequence

PGM2L1
NM_173582.6 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.709

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 Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005956918).

BP6

Variant 11-74342528-G-A is Benign according to our data. Variant chr11-74342528-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3034165.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00137 (209/152200) while in subpopulation NFE AF= 0.00229 (156/68000). AF 95% confidence interval is 0.002. There are 0 homozygotes in gnomad4. There are 91 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
PGM2L1	NM_173582.6 linkuse as main transcript	c.1565C>T	p.Thr522Ile	missense_variant	12/14	ENST00000298198.5
LOC112268078	XR_002957258.2 linkuse as main transcript	n.314+13040G>A		intron_variant, non_coding_transcript_variant
PGM2L1	XM_011544953.4 linkuse as main transcript	c.1628C>T	p.Thr543Ile	missense_variant	13/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PGM2L1	ENST00000298198.5 linkuse as main transcript	c.1565C>T	p.Thr522Ile	missense_variant	12/14	1	NM_173582.6	P1

Frequencies

GnomAD3 genomes

AF:

0.00137

AC:

209

AN:

152086

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000676

Gnomad AMI

AF:

0.0132

Gnomad AMR

AF:

0.000524

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00229

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00126

AC:

313

AN:

248740

Hom.:

AF XY:

0.00129

AC XY:

174

AN XY:

134468

show subpopulations

Gnomad AFR exome

AF:

0.000496

Gnomad AMR exome

AF:

0.000501

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000334

Gnomad FIN exome

AF:

0.000278

Gnomad NFE exome

AF:

0.00246

Gnomad OTH exome

AF:

0.000660

GnomAD4 exome

AF:

0.00247

AC:

3598

AN:

1457384

Hom.:

Cov.:

AF XY:

0.00241

AC XY:

1744

AN XY:

724868

show subpopulations

Gnomad4 AFR exome

AF:

0.000842

Gnomad4 AMR exome

AF:

0.000429

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000469

Gnomad4 FIN exome

AF:

0.000281

Gnomad4 NFE exome

AF:

0.00311

Gnomad4 OTH exome

AF:

0.00131

GnomAD4 genome

AF:

0.00137

AC:

209

AN:

152200

Hom.:

Cov.:

AF XY:

0.00122

AC XY:

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.000674

Gnomad4 AMR

AF:

0.000523

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00229

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00224

Hom.:

Bravo

AF:

0.00164

TwinsUK

AF:

0.00324

AC:

ALSPAC

AF:

0.00415

AC:

ESP6500AA

AF:

0.000455

AC:

ESP6500EA

AF:

0.00280

AC:

ExAC

AF:

0.00126

AC:

153

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

PGM2L1-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 20, 2022

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.079

Eigen

Benign

-0.71

Eigen_PC

Benign

-0.63

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.33

M_CAP

Benign

0.0023

MetaRNN

Benign

0.0060

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.90

MutationTaster

Benign

1.0

PrimateAI

Benign

0.33

PROVEAN

Benign

-2.0

REVEL

Benign

0.044

Sift

Benign

0.059

Sift4G

Benign

0.15

Polyphen

0.0060

Vest4

0.14

MVP

0.19

MPC

0.60

ClinPred

0.0074

GERP RS

2.9

Varity_R

0.080

gMVP

0.39

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

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