rs724159972

Variant names:

• chr9-69013871-G-C
• rs724159972
• NM_002732.4:c.222C>G

Your query was ambiguous. Multiple possible variants found:

• chr9-69013871-G-C
• chr9-69013871-G-T

Variant summary

Our verdict is Likely pathogenic. The variant received 7 ACMG points: 7P and 0B. PM2 PP3_Strong PP5

The NM_002732.4(PRKACG):​c.222C>G​(p.Ile74Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 30)
• Consequence: PRKACG NM_002732.4 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 0.0890
• Publications: 5 publications found

Genes affected

PRKACG (HGNC:9382): (protein kinase cAMP-activated catalytic subunit gamma) Cyclic AMP-dependent protein kinase (PKA) consists of two catalytic subunits and a regulatory subunit dimer. This gene encodes the gamma form of its catalytic subunit. The gene is intronless and is thought to be a retrotransposon derived from the gene for the alpha form of the PKA catalytic subunit. [provided by RefSeq, Jul 2008]

PRKACG Gene-Disease associations (from GenCC):

• platelet-type bleeding disorder 19

  Inheritance: AR Classification: SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Likely_pathogenic. The variant received 7 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.942
• PP5: Variant 9-69013871-G-C is Pathogenic according to our data. Variant chr9-69013871-G-C is described in ClinVar as Pathogenic. ClinVar VariationId is 162394.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKACG	NM_002732.4	c.222C>G	p.Ile74Met	missense_variant	Exon 1 of 1	ENST00000377276.5	NP_002723.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKACG	ENST00000377276.5	c.222C>G	p.Ile74Met	missense_variant	Exon 1 of 1	6	NM_002732.4	ENSP00000366488.2

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 30

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Platelet-type bleeding disorder 19 Pathogenic:1

Oct 16, 2014

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	17
DANN	Benign	0.96
DEOGEN2	Benign	0.19	T
Eigen	Benign	-0.70
Eigen_PC	Benign	-0.99
FATHMM_MKL	Benign	0.047	N
LIST_S2	Uncertain	0.95	D
M_CAP	Pathogenic	0.43	D
MetaRNN	Pathogenic	0.94	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L
PhyloP100		0.089
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-2.2	N
REVEL	Pathogenic	0.69
Sift	Benign	0.030	D
Sift4G	Benign	0.16	T
Polyphen		0.98	D
Vest4		0.73
MutPred		0.76		Gain of disorder (P = 0.0361);
MVP		0.33
MPC		0.95
ClinPred		0.42	T
GERP RS		-2.6
PromoterAI		-0.060	Neutral
Varity_R		0.22
gMVP		0.28
Mutation Taster		=84/16	disease causing (ClinVar)

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

Other links and lift over

dbSNP: rs724159972; hg19: chr9-71628787;