Variant 2-219283125-G-A 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_006736.6(DNAJB2):c.446-8G>A variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0343 in 1,613,938 control chromosomes in the GnomAD database, including 3,924 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.096 ( 1698 hom., cov: 32)

Exomes 𝑓: 0.028 ( 2226 hom. )

Consequence

DNAJB2
NM_006736.6 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.0002655

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -1.90

Variant links:

Genes affected

DNAJB2 (HGNC:5228): (DnaJ heat shock protein family (Hsp40) member B2) This gene is almost exclusively expressed in the brain, mainly in the neuronal layers. It encodes a protein that shows sequence similarity to bacterial DnaJ protein and the yeast homologs. In bacteria, this protein is implicated in protein folding and protein complex dissociation. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Jul 2011]

DNAJB2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant 2-219283125-G-A is Benign according to our data. Variant chr2-219283125-G-A is described in ClinVar as [Benign]. Clinvar id is 473303.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-219283125-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.273 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAJB2	NM_006736.6 linkuse as main transcript	c.446-8G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000336576.10	NP_006727.2
DNAJB2	NM_001039550.2 linkuse as main transcript	c.446-8G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant			NP_001034639.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAJB2	ENST00000336576.10 linkuse as main transcript	c.446-8G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_006736.6	ENSP00000338019		P25686-3

Frequencies

GnomAD3 genomes

AF:

0.0959

AC:

14581

AN:

152078

Hom.:

1684

Cov.:

show subpopulations

Gnomad AFR

AF:

0.277

Gnomad AMI

AF:

0.00768

Gnomad AMR

AF:

0.0424

Gnomad ASJ

AF:

0.0314

Gnomad EAS

AF:

0.127

Gnomad SAS

AF:

0.0108

Gnomad FIN

AF:

0.0175

Gnomad MID

AF:

0.0538

Gnomad NFE

AF:

0.0188

Gnomad OTH

AF:

0.0783

GnomAD3 exomes

AF:

0.0446

AC:

11194

AN:

251040

Hom.:

871

AF XY:

0.0387

AC XY:

5252

AN XY:

135744

show subpopulations

Gnomad AFR exome

AF:

0.281

Gnomad AMR exome

AF:

0.0238

Gnomad ASJ exome

AF:

0.0339

Gnomad EAS exome

AF:

0.125

Gnomad SAS exome

AF:

0.00846

Gnomad FIN exome

AF:

0.0192

Gnomad NFE exome

AF:

0.0200

Gnomad OTH exome

AF:

0.0375

GnomAD4 exome

AF:

0.0279

AC:

40800

AN:

1461742

Hom.:

2226

Cov.:

AF XY:

0.0264

AC XY:

19199

AN XY:

727186

show subpopulations

Gnomad4 AFR exome

AF:

0.284

Gnomad4 AMR exome

AF:

0.0264

Gnomad4 ASJ exome

AF:

0.0312

Gnomad4 EAS exome

AF:

0.147

Gnomad4 SAS exome

AF:

0.00863

Gnomad4 FIN exome

AF:

0.0178

Gnomad4 NFE exome

AF:

0.0169

Gnomad4 OTH exome

AF:

0.0447

GnomAD4 genome

AF:

0.0962

AC:

14634

AN:

152196

Hom.:

1698

Cov.:

AF XY:

0.0935

AC XY:

6961

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.277

Gnomad4 AMR

AF:

0.0423

Gnomad4 ASJ

AF:

0.0314

Gnomad4 EAS

AF:

0.127

Gnomad4 SAS

AF:

0.0106

Gnomad4 FIN

AF:

0.0175

Gnomad4 NFE

AF:

0.0188

Gnomad4 OTH

AF:

0.0789

Alfa

AF:

0.0490

Hom.:

481

Bravo

AF:

0.107

Asia WGS

AF:

0.0780

AC:

269

AN:

3478

EpiCase

AF:

0.0194

EpiControl

AF:

0.0184

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Charcot-Marie-Tooth disease

Benign:1

Benign, criteria provided, single submitter

clinical testing

Molecular Genetics Laboratory, London Health Sciences Centre

- -

Neuronopathy, distal hereditary motor, autosomal recessive 5

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

0.50

DANN

Benign

0.88

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00027

dbscSNV1_RF

Benign

0.14

SpliceAI score (max)

0.020

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