2-219279688-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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:2
• Conservation: PhyloP100: 0.380

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]

ACMG classification

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	UniProt
DNAJB2	NM_006736.6	c.-36-110G>C		intron_variant		ENST00000336576.10
DNAJB2	NM_001039550.2	c.-36-110G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAJB2	ENST00000336576.10	c.-36-110G>C		intron_variant		1	NM_006736.6

Frequencies

GnomAD3 genomes AF: 0.232 AC: 35319 AN: 152042 Hom.: 5026 Cov.: 33

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.: 9 AF XY: 0.184 AC XY: 61517 AN XY: 333988

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.: 33 AF XY: 0.228 AC XY: 16942 AN XY: 74384

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:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

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

Other links and lift over

dbSNP: rs908197; hg19: chr2-220144410; COSMIC: COSV60675462; COSMIC: COSV60675462;