rs61729452

Variant names:

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_000292.3(PHKA2):c.2532G>A(p.Leu844Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0139 in 1,182,524 control chromosomes in the GnomAD database, including 96 homozygotes. There are 5,145 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0092 ( 7 hom., 270 hem., cov: 23)

Exomes 𝑓: 0.014 ( 89 hom. 4875 hem. )

Consequence

PHKA2
NM_000292.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.752

Variant links:

Genes affected

PHKA2 (HGNC:8926): (phosphorylase kinase regulatory subunit alpha 2) Phosphorylase kinase is a polymer of 16 subunits, four each of alpha, beta, gamma and delta. The alpha subunit includes the skeletal muscle and hepatic isoforms, and the hepatic isoform is encoded by this gene. The beta subunit is the same in both the muscle and hepatic isoforms, and encoded by one gene. The gamma subunit also includes the skeletal muscle and hepatic isoforms, which are encoded by two different genes. The delta subunit is a calmodulin and can be encoded by three different genes. The gamma subunits contain the active site of the enzyme, whereas the alpha and beta subunits have regulatory functions controlled by phosphorylation. The delta subunit mediates the dependence of the enzyme on calcium concentration. Mutations in this gene cause glycogen storage disease type 9A, also known as X-linked liver glycogenosis. Alternatively spliced transcript variants have been reported, but the full-length nature of these variants has not been determined.[provided by RefSeq, Feb 2010]

PHKA2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.45).

BP6

Variant X-18907083-C-T is Benign according to our data. Variant chrX-18907083-C-T is described in ClinVar as [Benign]. Clinvar id is 255774.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-18907083-C-T is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=0.752 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00924 (1037/112242) while in subpopulation NFE AF= 0.0157 (836/53160). AF 95% confidence interval is 0.0148. There are 7 homozygotes in gnomad4. There are 270 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 7 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHKA2	NM_000292.3 link	c.2532G>A	p.Leu844Leu	synonymous_variant	Exon 23 of 33	ENST00000379942.5	NP_000283.1	P46019

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHKA2	ENST00000379942.5 link	c.2532G>A	p.Leu844Leu	synonymous_variant	Exon 23 of 33	1	NM_000292.3	ENSP00000369274.4		P46019

Frequencies

GnomAD3 genomes

AF:

0.00924

AC:

1037

AN:

112186

Hom.:

Cov.:

AF XY:

0.00786

AC XY:

270

AN XY:

34332

show subpopulations

Gnomad AFR

AF:

0.00204

Gnomad AMI

AF:

0.00586

Gnomad AMR

AF:

0.00508

Gnomad ASJ

AF:

0.00452

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00371

Gnomad FIN

AF:

0.00729

Gnomad MID

AF:

0.00424

Gnomad NFE

AF:

0.0157

Gnomad OTH

AF:

0.00797

GnomAD3 exomes

AF:

0.00939

AC:

1297

AN:

138133

Hom.:

AF XY:

0.00951

AC XY:

410

AN XY:

43101

show subpopulations

Gnomad AFR exome

AF:

0.00201

Gnomad AMR exome

AF:

0.00367

Gnomad ASJ exome

AF:

0.00452

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00470

Gnomad FIN exome

AF:

0.00972

Gnomad NFE exome

AF:

0.0163

Gnomad OTH exome

AF:

0.00978

GnomAD4 exome

AF:

0.0143

AC:

15344

AN:

1070282

Hom.:

Cov.:

AF XY:

0.0141

AC XY:

4875

AN XY:

345606

show subpopulations

Gnomad4 AFR exome

AF:

0.00217

Gnomad4 AMR exome

AF:

0.00389

Gnomad4 ASJ exome

AF:

0.00408

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00455

Gnomad4 FIN exome

AF:

0.0117

Gnomad4 NFE exome

AF:

0.0168

Gnomad4 OTH exome

AF:

0.0111

GnomAD4 genome

AF:

0.00924

AC:

1037

AN:

112242

Hom.:

Cov.:

AF XY:

0.00785

AC XY:

270

AN XY:

34398

show subpopulations

Gnomad4 AFR

AF:

0.00204

Gnomad4 AMR

AF:

0.00507

Gnomad4 ASJ

AF:

0.00452

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00372

Gnomad4 FIN

AF:

0.00729

Gnomad4 NFE

AF:

0.0157

Gnomad4 OTH

AF:

0.00786

Alfa

AF:

0.0117

Hom.:

Bravo

AF:

0.00887

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Oct 18, 2016

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Glycogen storage disease IXa1

Benign:1

Jan 24, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.45

CADD

Benign

3.0

DANN

Benign

0.59

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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