Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_000292.3(PHKA2):c.2365C>T(p.Pro789Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000121 in 1,208,972 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 35 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
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]
Our verdict: Benign. The variant received -20 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.025713265).
BP6
Variant X-18908052-G-A is Benign according to our data. Variant chrX-18908052-G-A is described in CliVar as Likely_benign. Clinvar id is 445969.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-18908052-G-A is described in CliVar as Likely_benign. Clinvar id is 445969.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-18908052-G-A is described in CliVar as Likely_benign. Clinvar id is 445969.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-18908052-G-A is described in CliVar as Likely_benign. Clinvar id is 445969.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-18908052-G-A is described in CliVar as Likely_benign. Clinvar id is 445969.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-18908052-G-A is described in CliVar as Likely_benign. Clinvar id is 445969.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-18908052-G-A is described in CliVar as Likely_benign. Clinvar id is 445969.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-18908052-G-A is described in CliVar as Likely_benign. Clinvar id is 445969.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-18908052-G-A is described in CliVar as Likely_benign. Clinvar id is 445969.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-18908052-G-A is described in CliVar as Likely_benign. Clinvar id is 445969.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-18908052-G-A is described in CliVar as Likely_benign. Clinvar id is 445969.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-18908052-G-A is described in CliVar as Likely_benign. Clinvar id is 445969.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-18908052-G-A is described in CliVar as Likely_benign. Clinvar id is 445969.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-18908052-G-A is described in CliVar as Likely_benign. Clinvar id is 445969.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-18908052-G-A is described in CliVar as Likely_benign. Clinvar id is 445969.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-18908052-G-A is described in CliVar as Likely_benign. Clinvar id is 445969.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-18908052-G-A is described in CliVar as Likely_benign. Clinvar id is 445969.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-18908052-G-A is described in CliVar as Likely_benign. Clinvar id is 445969.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-18908052-G-A is described in CliVar as Likely_benign. Clinvar id is 445969.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-18908052-G-A is described in CliVar as Likely_benign. Clinvar id is 445969.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-18908052-G-A is described in CliVar as Likely_benign. Clinvar id is 445969.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-18908052-G-A is described in CliVar as Likely_benign. Clinvar id is 445969.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-18908052-G-A is described in CliVar as Likely_benign. Clinvar id is 445969.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-18908052-G-A is described in CliVar as Likely_benign. Clinvar id is 445969.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-18908052-G-A is described in CliVar as Likely_benign. Clinvar id is 445969.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000643 (72/112029) while in subpopulation AFR AF = 0.0022 (68/30852). AF 95% confidence interval is 0.00178. There are 0 homozygotes in GnomAd4. There are 19 alleles in the male GnomAd4 subpopulation. Median coverage is 23. This position passed quality control check.
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). -
not providedBenign:1
May 15, 2017
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics