Variant chr2-219279688-G-C 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.-36-110G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 793,828 control chromosomes in the GnomAD database, including 17,047 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 5049 hom., cov: 33)

Exomes 𝑓: 0.18 ( 11998 hom. )

Consequence

DNAJB2
NM_006736.6 intron

Scores

Splicing: ADA: 0.00002769

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.380

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=-0.94).

BP6

Variant 2-219279688-G-C is Benign according to our data. Variant chr2-219279688-G-C is described in ClinVar as [Benign]. Clinvar id is 680749.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.395 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.-36-110G>C		intron_variant		ENST00000336576.10	NP_006727.2	P25686-3
DNAJB2	NM_001039550.2 linkuse as main transcript	c.-36-110G>C		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.-36-110G>C		intron_variant		1	NM_006736.6	ENSP00000338019.5		P25686-3

Frequencies

GnomAD3 genomes

AF:

0.232

AC:

35319

AN:

152042

Hom.:

5026

Cov.:

show subpopulations

Gnomad AFR

AF:

0.399

Gnomad AMI

AF:

0.169

Gnomad AMR

AF:

0.195

Gnomad ASJ

AF:

0.217

Gnomad EAS

AF:

0.151

Gnomad SAS

AF:

0.218

Gnomad FIN

AF:

0.0746

Gnomad MID

AF:

0.285

Gnomad NFE

AF:

0.172

Gnomad OTH

AF:

0.249

GnomAD4 exome

AF:

0.184

AC:

117747

AN:

641668

Hom.:

11998

Cov.:

AF XY:

0.184

AC XY:

61517

AN XY:

333988

show subpopulations

Gnomad4 AFR exome

AF:

0.397

Gnomad4 AMR exome

AF:

0.163

Gnomad4 ASJ exome

AF:

0.227

Gnomad4 EAS exome

AF:

0.151

Gnomad4 SAS exome

AF:

0.213

Gnomad4 FIN exome

AF:

0.0858

Gnomad4 NFE exome

AF:

0.178

Gnomad4 OTH exome

AF:

0.209

GnomAD4 genome

AF:

0.232

AC:

35364

AN:

152160

Hom.:

5049

Cov.:

AF XY:

0.228

AC XY:

16942

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.400

Gnomad4 AMR

AF:

0.194

Gnomad4 ASJ

AF:

0.217

Gnomad4 EAS

AF:

0.151

Gnomad4 SAS

AF:

0.219

Gnomad4 FIN

AF:

0.0746

Gnomad4 NFE

AF:

0.172

Gnomad4 OTH

AF:

0.246

Alfa

AF:

0.0743

Hom.:

114

Bravo

AF:

0.250

Asia WGS

AF:

0.172

AC:

600

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

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	Jun 14, 2018	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. -

Neuronopathy, distal hereditary motor, autosomal recessive 5

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

4.8

DANN

Benign

0.45

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000028

dbscSNV1_RF

Benign

0.0060

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