rs756863425

Variant names:

• chr2-218340130-C-A
• rs756863425
• NM_015488.5:c.454C>A

Your query was ambiguous. Multiple possible variants found:

• chr2-218340130-C-A
• chr2-218340130-C-G
• chr2-218340130-C-T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_015488.5(PNKD):​c.454C>A​(p.Arg152Arg) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PNKD NM_015488.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.71
• Publications: 0 publications found

Genes affected

PNKD (HGNC:9153): (PNKD metallo-beta-lactamase domain containing) This gene is thought to play a role in the regulation of myofibrillogenesis. Mutations in this gene have been associated with the movement disorder paroxysmal non-kinesigenic dyskinesia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2010]

CATIP-AS2 (HGNC:41079): (CATIP antisense RNA 2)

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.3).
• BP7: Synonymous conserved (PhyloP=2.71 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015488.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PNKD	NM_015488.5	MANE Select	c.454C>A	p.Arg152Arg	synonymous	Exon 4 of 10	NP_056303.3
	PNKD	NM_022572.4		c.382C>A	p.Arg128Arg	synonymous	Exon 3 of 9	NP_072094.1
	CATIP-AS2	NR_125777.1		n.120+11030G>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PNKD	ENST00000273077.9	TSL:1 MANE Select	c.454C>A	p.Arg152Arg	synonymous	Exon 4 of 10	ENSP00000273077.4
	PNKD	ENST00000258362.7	TSL:1	c.382C>A	p.Arg128Arg	synonymous	Exon 3 of 9	ENSP00000258362.3
	PNKD	ENST00000685415.1		c.571C>A	p.Arg191Arg	synonymous	Exon 5 of 11	ENSP00000510415.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
CADD	Benign	14
DANN	Benign	0.85
PhyloP100		2.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism

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: rs756863425; hg19: chr2-219204853; COSMIC: COSV51231403; COSMIC: COSV51231403;