rs193920924

Variant names:

• chr9-110136169-G-T
• rs193920924
• NM_007203.5:c.625G>T

Your query was ambiguous. Multiple possible variants found:

• chr9-110136169-G-T
• chr9-110136169-G-A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_007203.5(PALM2AKAP2):​c.625G>T​(p.Glu209*) variant causes a stop gained 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 Uncertain significance (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PALM2AKAP2 NM_007203.5 stop_gained
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 0.781
• Publications: 3 publications found

Genes affected

PALM2AKAP2 (HGNC:33529): (PALM2 and AKAP2 fusion) This gene belongs to the paralemmin downstream gene (PDG) family defined in PMID:22855693. Paralemmin downstream genes may have evolved contiguously with the paralemmin genes and are associated with other paralemmin paralogs in humans and several other taxa. The gene encodes three distinct protein isoforms, the PALM2 isoform, the AKAP2 isoform and the PALM2-AKAP2 isoform. The biological significance of the PALM2-AKAP2 isoforms is yet unknown. Earlier, PALM2 and AKAP2 were annotated as separate genes and PALM2-AKAP2 was annotated as a readthrough gene. [provided by RefSeq, May 2019]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007203.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PALM2AKAP2	NM_007203.5	MANE Select	c.625G>T	p.Glu209*	stop_gained	Exon 8 of 11	NP_009134.1	Q9Y2D5-4
	PALM2AKAP2	NM_147150.3		c.625G>T	p.Glu209*	stop_gained	Exon 8 of 10	NP_671492.1	Q9Y2D5-6
	PALM2AKAP2	NM_001198656.1		c.199G>T	p.Glu67*	stop_gained	Exon 2 of 5	NP_001185585.1	Q9Y2D5-7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PALM2AKAP2	ENST00000374530.8	TSL:2 MANE Select	c.625G>T	p.Glu209*	stop_gained	Exon 8 of 11	ENSP00000363654.3	Q9Y2D5-4
	PALM2AKAP2	ENST00000434623.6	TSL:1	c.199G>T	p.Glu67*	stop_gained	Exon 2 of 5	ENSP00000404782.2	Q9Y2D5-7
	PALM2AKAP2	ENST00000374525.5	TSL:1	c.199G>T	p.Glu67*	stop_gained	Exon 2 of 4	ENSP00000363649.1	Q9Y2D5-5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	1	-	Prostate cancer (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.29	D
BayesDel_noAF	Pathogenic	0.17
CADD	Pathogenic	26
DANN	Benign	0.97
Eigen	Benign	0.062
Eigen_PC	Benign	-0.31
FATHMM_MKL	Benign	0.15	N
PhyloP100		0.78
Vest4		0.37
GERP RS		-1.3
Mutation Taster		=24/176	disease causing (fs/PTC)

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: rs193920924; hg19: chr9-112898449; COSMIC: COSV52180058; COSMIC: COSV52180058;