chr2-218344961-GATATGC-G

Variant names:

• chr2-218344961-GATATGC-G
• rs576363906
• NM_015488.5:c.1140_1145delTATGCA

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 3P and 12B. PM4 PP3 BP6_Very_Strong BS2

The NM_015488.5(PNKD):​c.1140_1145delTATGCA​(p.Met381_His382del) variant causes a disruptive inframe deletion change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00115 in 1,613,744 control chromosomes in the GnomAD database, including 3 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00070 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0012 (3 hom.)
• Consequence: PNKD NM_015488.5 disruptive_inframe_deletion
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• 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: Benign. The variant received -9 ACMG points.

• 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
• BP6: Variant 2-218344961-GATATGC-G is Benign according to our data. Variant chr2-218344961-GATATGC-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 334329.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 107 AD gene.

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_1145delTATGCA	p.Met381_His382del	disruptive_inframe_deletion	Exon 10 of 10	NP_056303.3
	PNKD	NM_022572.4		c.1068_1073delTATGCA	p.Met357_His358del	disruptive_inframe_deletion	Exon 9 of 9	NP_072094.1	Q8N490-3
	CATIP-AS2	NR_125777.1		n.120+6193_120+6198delGCATAT		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_1145delTATGCA	p.Met381_His382del	disruptive_inframe_deletion	Exon 10 of 10	ENSP00000273077.4	Q8N490-1
	PNKD	ENST00000258362.7	TSL:1	c.1068_1073delTATGCA	p.Met357_His358del	disruptive_inframe_deletion	Exon 9 of 9	ENSP00000258362.3	Q8N490-3
	PNKD	ENST00000685415.1		c.1257_1262delTATGCA	p.Met420_His421del	disruptive_inframe_deletion	Exon 11 of 11	ENSP00000510415.1	A0A8I5KXK0

Frequencies

GnomAD3 genomes AF: 0.000703 AC: 107 AN: 152138 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000982

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000660

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00115

Gnomad OTH AF: 0.000956

GnomAD2 exomes AF: 0.000595 AC: 148 AN: 248688 AF XY: 0.000637

Gnomad AFR exome AF: 0.000194

Gnomad AMR exome AF: 0.000203

Gnomad ASJ exome AF: 0.000100

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000556

Gnomad NFE exome AF: 0.00107

Gnomad OTH exome AF: 0.000827

GnomAD4 exome AF: 0.00119 AC: 1745 AN: 1461488 Hom.: 3 AF XY: 0.00113 AC XY: 825 AN XY: 727044

African (AFR) AF: 0.0000598 AC: 2 AN: 33472

American (AMR) AF: 0.000201 AC: 9 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26106

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86246

European-Finnish (FIN) AF: 0.000394 AC: 21 AN: 53258

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5740

European-Non Finnish (NFE) AF: 0.00150 AC: 1669 AN: 1111882

Other (OTH) AF: 0.000712 AC: 43 AN: 60384

GnomAD4 genome AF: 0.000703 AC: 107 AN: 152256 Hom.: 0 Cov.: 33 AF XY: 0.000618 AC XY: 46 AN XY: 74452

African (AFR) AF: 0.000120 AC: 5 AN: 41542

American (AMR) AF: 0.000981 AC: 15 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.000660 AC: 7 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00115 AC: 78 AN: 68012

Other (OTH) AF: 0.000946 AC: 2 AN: 2114

Alfa AF: 0.000203 Hom.: 0

Bravo AF: 0.000642

EpiCase AF: 0.00109

EpiControl AF: 0.000830

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Paroxysmal nonkinesigenic dyskinesia (1)
-	-	1	Paroxysmal nonkinesigenic dyskinesia 1 (1)
-	-	1	PNKD-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		9.0
Mutation Taster		=78/122	disease causing

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;