Variant 2-219280564-C-T 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.66-14C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 1,606,996 control chromosomes in the GnomAD database, including 34,076 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.26 ( 6571 hom., cov: 32)

Exomes 𝑓: 0.18 ( 27505 hom. )

Consequence

DNAJB2
NM_006736.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.639

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:

DNAJB2 (HGNC:):

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=-0.56).

BP6

Variant 2-219280564-C-T is Benign according to our data. Variant chr2-219280564-C-T is described in ClinVar as [Benign]. Clinvar id is 137118.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-219280564-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.476 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.66-14C>T		intron_variant		ENST00000336576.10	NP_006727.2	P25686-3
DNAJB2	NM_001039550.2 linkuse as main transcript	c.66-14C>T		intron_variant			NP_001034639.1	P25686-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAJB2	ENST00000336576.10 linkuse as main transcript	c.66-14C>T		intron_variant		1	NM_006736.6	ENSP00000338019.5		P25686-3

Frequencies

GnomAD3 genomes

AF:

0.256

AC:

38899

AN:

151934

Hom.:

6552

Cov.:

show subpopulations

Gnomad AFR

AF:

0.482

Gnomad AMI

AF:

0.169

Gnomad AMR

AF:

0.205

Gnomad ASJ

AF:

0.218

Gnomad EAS

AF:

0.151

Gnomad SAS

AF:

0.218

Gnomad FIN

AF:

0.0744

Gnomad MID

AF:

0.288

Gnomad NFE

AF:

0.172

Gnomad OTH

AF:

0.270

GnomAD3 exomes

AF:

0.188

AC:

46998

AN:

250174

Hom.:

5434

AF XY:

0.186

AC XY:

25127

AN XY:

135332

show subpopulations

Gnomad AFR exome

AF:

0.490

Gnomad AMR exome

AF:

0.154

Gnomad ASJ exome

AF:

0.228

Gnomad EAS exome

AF:

0.152

Gnomad SAS exome

AF:

0.209

Gnomad FIN exome

AF:

0.0812

Gnomad NFE exome

AF:

0.171

Gnomad OTH exome

AF:

0.199

GnomAD4 exome

AF:

0.184

AC:

267970

AN:

1454944

Hom.:

27505

Cov.:

AF XY:

0.184

AC XY:

133300

AN XY:

724392

show subpopulations

Gnomad4 AFR exome

AF:

0.493

Gnomad4 AMR exome

AF:

0.160

Gnomad4 ASJ exome

AF:

0.224

Gnomad4 EAS exome

AF:

0.153

Gnomad4 SAS exome

AF:

0.212

Gnomad4 FIN exome

AF:

0.0832

Gnomad4 NFE exome

AF:

0.177

Gnomad4 OTH exome

AF:

0.213

GnomAD4 genome

AF:

0.256

AC:

38943

AN:

152052

Hom.:

6571

Cov.:

AF XY:

0.251

AC XY:

18674

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.482

Gnomad4 AMR

AF:

0.205

Gnomad4 ASJ

AF:

0.218

Gnomad4 EAS

AF:

0.151

Gnomad4 SAS

AF:

0.219

Gnomad4 FIN

AF:

0.0744

Gnomad4 NFE

AF:

0.172

Gnomad4 OTH

AF:

0.267

Alfa

AF:

0.208

Hom.:

1305

Bravo

AF:

0.277

Asia WGS

AF:

0.176

AC:

613

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

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	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 30, 2021	- -

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. -

Charcot-Marie-Tooth disease

Benign:1

Benign, criteria provided, single submitter

clinical testing

Molecular Genetics Laboratory, London Health Sciences Centre

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Benign

0.87

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