Variant chr2-218275662-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_015488.5(PNKD):c.236+4113A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0671 in 1,590,754 control chromosomes in the GnomAD database, including 4,133 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.052 ( 283 hom., cov: 32)

Exomes 𝑓: 0.069 ( 3850 hom. )

Consequence

PNKD
NM_015488.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0140

Variant links:

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]

PNKD links:

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]

TMBIM1 links:

TMBIM1 (HGNC:):

TMBIM1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

This place is a probable branch point but likely benign (scored 2 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 2-218275662-A-G is Benign according to our data. Variant chr2-218275662-A-G is described in ClinVar as [Benign]. Clinvar id is 1241809.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0767 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PNKD	NM_015488.5 linkuse as main transcript	c.236+4113A>G		intron_variant		ENST00000273077.9	NP_056303.3	Q8N490-1A0A024R415
TMBIM1	NM_022152.6 linkuse as main transcript	c.790-41T>C		intron_variant		ENST00000258412.8	NP_071435.2	Q969X1B3KSM0A0A024R472

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PNKD	ENST00000273077.9 linkuse as main transcript	c.236+4113A>G		intron_variant		1	NM_015488.5	ENSP00000273077.4		Q8N490-1
TMBIM1	ENST00000258412.8 linkuse as main transcript	c.790-41T>C		intron_variant		1	NM_022152.6	ENSP00000258412.3		Q969X1

Frequencies

GnomAD3 genomes

AF:

0.0520

AC:

7916

AN:

152180

Hom.:

283

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0137

Gnomad AMI

AF:

0.0143

Gnomad AMR

AF:

0.0478

Gnomad ASJ

AF:

0.0730

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0122

Gnomad FIN

AF:

0.0784

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.0785

Gnomad OTH

AF:

0.0523

GnomAD3 exomes

AF:

0.0546

AC:

12534

AN:

229478

Hom.:

458

AF XY:

0.0554

AC XY:

6851

AN XY:

123682

show subpopulations

Gnomad AFR exome

AF:

0.0112

Gnomad AMR exome

AF:

0.0366

Gnomad ASJ exome

AF:

0.0851

Gnomad EAS exome

AF:

0.000167

Gnomad SAS exome

AF:

0.0171

Gnomad FIN exome

AF:

0.0793

Gnomad NFE exome

AF:

0.0783

Gnomad OTH exome

AF:

0.0597

GnomAD4 exome

AF:

0.0687

AC:

98793

AN:

1438456

Hom.:

3850

Cov.:

AF XY:

0.0674

AC XY:

48162

AN XY:

714252

show subpopulations

Gnomad4 AFR exome

AF:

0.0103

Gnomad4 AMR exome

AF:

0.0373

Gnomad4 ASJ exome

AF:

0.0809

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.0157

Gnomad4 FIN exome

AF:

0.0788

Gnomad4 NFE exome

AF:

0.0778

Gnomad4 OTH exome

AF:

0.0620

GnomAD4 genome

AF:

0.0520

AC:

7914

AN:

152298

Hom.:

283

Cov.:

AF XY:

0.0502

AC XY:

3737

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.0136

Gnomad4 AMR

AF:

0.0477

Gnomad4 ASJ

AF:

0.0730

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0122

Gnomad4 FIN

AF:

0.0784

Gnomad4 NFE

AF:

0.0785

Gnomad4 OTH

AF:

0.0517

Alfa

AF:

0.0375

Hom.:

Bravo

AF:

0.0488

Asia WGS

AF:

0.00895

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 14, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.68

DANN

Benign

0.42

BranchPoint Hunter

2.0

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over