rs61733281

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7

The NM_000292.3(PHKA2):​c.2436G>T​(p.Gly812Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars). Synonymous variant affecting the same amino acid position (i.e. G812G) has been classified as Benign.

Frequency

Genomes: not found (cov: 23)

Consequence

PHKA2
NM_000292.3 synonymous

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.11

Publications

1 publications found
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 Gene-Disease associations (from GenCC):
  • glycogen storage disease IXa1
    Inheritance: XL Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Ambry Genetics
  • glycogen storage disease due to liver phosphorylase kinase deficiency
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

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ACMG classification

Classification was made for transcript

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=-0.67).
BP7
Synonymous conserved (PhyloP=-1.11 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000292.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
PHKA2
NM_000292.3
MANE Select
c.2436G>Tp.Gly812Gly
synonymous
Exon 22 of 33NP_000283.1P46019
PHKA2
NM_001440805.1
c.2436G>Tp.Gly812Gly
synonymous
Exon 22 of 33NP_001427734.1
PHKA2
NM_001440800.1
c.2436G>Tp.Gly812Gly
synonymous
Exon 22 of 32NP_001427729.1

Ensembl Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
PHKA2
ENST00000379942.5
TSL:1 MANE Select
c.2436G>Tp.Gly812Gly
synonymous
Exon 22 of 33ENSP00000369274.4P46019
PHKA2
ENST00000897868.1
c.2436G>Tp.Gly812Gly
synonymous
Exon 22 of 33ENSP00000567927.1
PHKA2
ENST00000954730.1
c.2421G>Tp.Gly807Gly
synonymous
Exon 22 of 33ENSP00000624789.1

Frequencies

GnomAD3 genomes
Cov.:
23
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
23
Alfa
AF:
0.00
Hom.:
96
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.67
CADD
Benign
3.1
DANN
Benign
0.49
PhyloP100
-1.1
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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

Other links and lift over

dbSNP: rs61733281; hg19: chrX-18926099; API
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