rs140805390

Positions:

chr2-219284799-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 2P and 14B. PM2BP4_ModerateBP6_Very_StrongBS1

The NM_006736.6(DNAJB2):c.787C>T(p.Leu263=) variant causes a synonymous change. The variant allele was found at a frequency of 0.000582 in 1,613,076 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00055 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00059 ( 0 hom. )

Consequence

DNAJB2
NM_006736.6 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 3.87

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 -12 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.35).

BP6

Variant 2-219284799-C-T is Benign according to our data. Variant chr2-219284799-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 377780.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-219284799-C-T is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4_exome allele frequency = 0.000585 (855/1460708) while in subpopulation NFE AF= 0.000652 (725/1111664). AF 95% confidence interval is 0.000612. There are 0 homozygotes in gnomad4_exome. There are 409 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAJB2	NM_006736.6 linkuse as main transcript	c.787C>T	p.Leu263=	synonymous_variant	9/9	ENST00000336576.10
DNAJB2	NM_001039550.2 linkuse as main transcript	c.787C>T	p.Leu263=	synonymous_variant	9/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAJB2	ENST00000336576.10 linkuse as main transcript	c.787C>T	p.Leu263=	synonymous_variant	9/9	1	NM_006736.6		P25686-3

Frequencies

GnomAD3 genomes

AF:

0.000552

AC:

AN:

152250

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00376

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000603

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000456

AC:

113

AN:

247944

Hom.:

AF XY:

0.000431

AC XY:

AN XY:

134550

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00226

Gnomad NFE exome

AF:

0.000573

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.000585

AC:

855

AN:

1460708

Hom.:

Cov.:

AF XY:

0.000563

AC XY:

409

AN XY:

726644

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00199

Gnomad4 NFE exome

AF:

0.000652

Gnomad4 OTH exome

AF:

0.000348

GnomAD4 genome

AF:

0.000551

AC:

AN:

152368

Hom.:

Cov.:

AF XY:

0.000684

AC XY:

AN XY:

74522

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00376

Gnomad4 NFE

AF:

0.000603

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000370

Hom.:

Bravo

AF:

0.000264

EpiCase

AF:

0.000763

EpiControl

AF:

0.000417

ClinVar

Significance: Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 21, 2017

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

Likely benign, criteria provided, single submitter

clinical testing

Molecular Genetics Laboratory, London Health Sciences Centre

- -

Inborn genetic diseases

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 11, 2019

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Aug 01, 2023

DNAJB2: BP4, BP7 -

Neuronopathy, distal hereditary motor, autosomal recessive 5

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jan 11, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.35

CADD

Benign

9.5

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