rs3731897

chr2-219281929-G-Achr2-219281929-G-T

Variant summary

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

The NM_006736.6(DNAJB2):c.230-10G>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 1,613,740 control chromosomes in the GnomAD database, including 22,708 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.16 ( 2231 hom., cov: 32)

Exomes 𝑓: 0.16 ( 20477 hom. )

Consequence

DNAJB2
NM_006736.6 splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.0008840

Clinical Significance

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

Conservation

PhyloP100: 0.458

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 2-219281929-G-A is Benign according to our data. Variant chr2-219281929-G-A is described in ClinVar as [Benign]. Clinvar id is 137119.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-219281929-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.197 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAJB2	NM_006736.6 linkuse as main transcript	c.230-10G>A		splice_polypyrimidine_tract_variant, intron_variant		ENST00000336576.10
DNAJB2	NM_001039550.2 linkuse as main transcript	c.230-10G>A		splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAJB2	ENST00000336576.10 linkuse as main transcript	c.230-10G>A		splice_polypyrimidine_tract_variant, intron_variant		1	NM_006736.6		P25686-3

Frequencies

GnomAD3 genomes

AF:

0.161

AC:

24519

AN:

152090

Hom.:

2226

Cov.:

show subpopulations

Gnomad AFR

AF:

0.194

Gnomad AMI

AF:

0.161

Gnomad AMR

AF:

0.165

Gnomad ASJ

AF:

0.195

Gnomad EAS

AF:

0.0498

Gnomad SAS

AF:

0.206

Gnomad FIN

AF:

0.0573

Gnomad MID

AF:

0.275

Gnomad NFE

AF:

0.159

Gnomad OTH

AF:

0.199

GnomAD3 exomes

AF:

0.148

AC:

37101

AN:

250998

Hom.:

3078

AF XY:

0.151

AC XY:

20517

AN XY:

135676

show subpopulations

Gnomad AFR exome

AF:

0.192

Gnomad AMR exome

AF:

0.135

Gnomad ASJ exome

AF:

0.207

Gnomad EAS exome

AF:

0.0544

Gnomad SAS exome

AF:

0.197

Gnomad FIN exome

AF:

0.0628

Gnomad NFE exome

AF:

0.157

Gnomad OTH exome

AF:

0.169

GnomAD4 exome

AF:

0.162

AC:

236702

AN:

1461532

Hom.:

20477

Cov.:

AF XY:

0.163

AC XY:

118594

AN XY:

727046

show subpopulations

Gnomad4 AFR exome

AF:

0.200

Gnomad4 AMR exome

AF:

0.139

Gnomad4 ASJ exome

AF:

0.204

Gnomad4 EAS exome

AF:

0.0467

Gnomad4 SAS exome

AF:

0.200

Gnomad4 FIN exome

AF:

0.0665

Gnomad4 NFE exome

AF:

0.165

Gnomad4 OTH exome

AF:

0.177

GnomAD4 genome

AF:

0.161

AC:

24525

AN:

152208

Hom.:

2231

Cov.:

AF XY:

0.158

AC XY:

11793

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.194

Gnomad4 AMR

AF:

0.164

Gnomad4 ASJ

AF:

0.195

Gnomad4 EAS

AF:

0.0493

Gnomad4 SAS

AF:

0.207

Gnomad4 FIN

AF:

0.0573

Gnomad4 NFE

AF:

0.159

Gnomad4 OTH

AF:

0.196

Alfa

AF:

0.158

Hom.:

2168

Bravo

AF:

0.171

Asia WGS

AF:

0.109

AC:

381

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Neuronopathy, distal hereditary motor, autosomal recessive 5

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 30, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -

Charcot-Marie-Tooth disease

Benign:1

Benign, criteria provided, single submitter

clinical testing

Molecular Genetics Laboratory, London Health Sciences Centre

- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 01, 2014

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

Cadd

Benign

7.4

Dann

Benign

0.71

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00088

dbscSNV1_RF

Benign

0.042

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