chr2-218344961-G-GATATGC

Variant names:

• chr2-218344961-G-GATATGC
• rs576363906
• NM_015488.5:c.1140_1145dupTATGCA

Variant summary

Our verdict is Uncertain significance. The variant received 5 ACMG points: 5P and 0B. PM2 PM4 PP3

The NM_015488.5(PNKD):​c.1140_1145dupTATGCA​(p.His382_Lys383insMetHis) variant causes a disruptive inframe insertion change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PNKD NM_015488.5 disruptive_inframe_insertion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.02
• Publications: 1 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: Uncertain_significance. The variant received 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_015488.5.
• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PNKD	NM_015488.5	MANE Select	c.1140_1145dupTATGCA	p.His382_Lys383insMetHis	disruptive_inframe_insertion	Exon 10 of 10	NP_056303.3
	PNKD	NM_022572.4		c.1068_1073dupTATGCA	p.His358_Lys359insMetHis	disruptive_inframe_insertion	Exon 9 of 9	NP_072094.1	Q8N490-3
	CATIP-AS2	NR_125777.1		n.120+6193_120+6198dupGCATAT		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PNKD	ENST00000273077.9	TSL:1 MANE Select	c.1140_1145dupTATGCA	p.His382_Lys383insMetHis	disruptive_inframe_insertion	Exon 10 of 10	ENSP00000273077.4	Q8N490-1
	PNKD	ENST00000258362.7	TSL:1	c.1068_1073dupTATGCA	p.His358_Lys359insMetHis	disruptive_inframe_insertion	Exon 9 of 9	ENSP00000258362.3	Q8N490-3
	PNKD	ENST00000685415.1		c.1257_1262dupTATGCA	p.His421_Lys422insMetHis	disruptive_inframe_insertion	Exon 11 of 11	ENSP00000510415.1	A0A8I5KXK0

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		9.0

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs576363906; hg19: chr2-219209684;