rs2382818

Variant names:

• chr2-218291184-A-T
• rs2382818
• NM_015488.5:c.236+19635A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015488.5(PNKD):​c.236+19635A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.36 in 151,756 control chromosomes in the GnomAD database, including 10,248 homozygotes. 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: 𝑓 0.36 (10248 hom., cov: 31)
• Consequence: PNKD NM_015488.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.824
• Publications: 17 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]

TMBIM1 (HGNC:23410): (transmembrane BAX inhibitor motif containing 1) Enables death receptor binding activity. Involved in negative regulation of Fas signaling pathway; negative regulation of extrinsic apoptotic signaling pathway via death domain receptors; and negative regulation of protein localization to plasma membrane. Located in Golgi apparatus; endosome membrane; and lysosomal membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.428 is higher than 0.05.

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.236+19635A>T		intron	N/A	NP_056303.3
	TMBIM1	NM_022152.6	MANE Select	c.-41+1282T>A		intron	N/A	NP_071435.2	Q969X1
	TMBIM1	NM_001321433.2		c.-139+1282T>A		intron	N/A	NP_001308362.1	Q969X1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PNKD	ENST00000273077.9	TSL:1 MANE Select	c.236+19635A>T		intron	N/A	ENSP00000273077.4	Q8N490-1
	TMBIM1	ENST00000258412.8	TSL:1 MANE Select	c.-41+1282T>A		intron	N/A	ENSP00000258412.3	Q969X1
	PNKD	ENST00000685415.1		c.353+18498A>T		intron	N/A	ENSP00000510415.1	A0A8I5KXK0

Frequencies

GnomAD3 genomes AF: 0.360 AC: 54639 AN: 151638 Hom.: 10247 Cov.: 31

Gnomad AFR AF: 0.244

Gnomad AMI AF: 0.447

Gnomad AMR AF: 0.438

Gnomad ASJ AF: 0.420

Gnomad EAS AF: 0.388

Gnomad SAS AF: 0.350

Gnomad FIN AF: 0.288

Gnomad MID AF: 0.529

Gnomad NFE AF: 0.417

Gnomad OTH AF: 0.400

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.360 AC: 54647 AN: 151756 Hom.: 10248 Cov.: 31 AF XY: 0.357 AC XY: 26497 AN XY: 74160

African (AFR) AF: 0.244 AC: 10127 AN: 41454

American (AMR) AF: 0.437 AC: 6662 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.420 AC: 1458 AN: 3468

East Asian (EAS) AF: 0.388 AC: 1994 AN: 5138

South Asian (SAS) AF: 0.350 AC: 1687 AN: 4814

European-Finnish (FIN) AF: 0.288 AC: 3036 AN: 10530

Middle Eastern (MID) AF: 0.528 AC: 152 AN: 288

European-Non Finnish (NFE) AF: 0.417 AC: 28284 AN: 67806

Other (OTH) AF: 0.400 AC: 845 AN: 2110

Alfa AF: 0.384 Hom.: 1443

Bravo AF: 0.368

Asia WGS AF: 0.316 AC: 1095 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.7
DANN	Benign	0.58
PhyloP100		-0.82
Mutation Taster		=100/0	polymorphism (auto)

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: rs2382818; hg19: chr2-219155907;