rs3731897

Variant names:

• chr2-219281929-G-A
• rs3731897
• NM_006736.6:c.230-10G>A

Your query was ambiguous. Multiple possible variants found:

• chr2-219281929-G-A
• chr2-219281929-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006736.6(DNAJB2):​c.230-10G>A variant causes a 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 intron
• Scores: Splicing: ADA: 0.0008840
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.458
• Publications: 8 publications found

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 Gene-Disease associations (from GenCC):

• Charcot-Marie-Tooth disease axonal type 2T

  Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
• neuronopathy, distal hereditary motor, autosomal recessive 5

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 137119.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.197 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006736.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAJB2	NM_006736.6	MANE Select	c.230-10G>A		intron	N/A	NP_006727.2
	DNAJB2	NM_001039550.2		c.230-10G>A		intron	N/A	NP_001034639.1	P25686-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAJB2	ENST00000336576.10	TSL:1 MANE Select	c.230-10G>A		intron	N/A	ENSP00000338019.5	P25686-3
	DNAJB2	ENST00000933785.1		c.230-10G>A		intron	N/A	ENSP00000603844.1
	DNAJB2	ENST00000392086.8	TSL:2	c.230-10G>A		intron	N/A	ENSP00000375936.4	P25686-2

Frequencies

GnomAD3 genomes AF: 0.161 AC: 24519 AN: 152090 Hom.: 2226 Cov.: 32

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

GnomAD2 exomes AF: 0.148 AC: 37101 AN: 250998 AF XY: 0.151

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 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.: 33 AF XY: 0.163 AC XY: 118594 AN XY: 727046

African (AFR) AF: 0.200 AC: 6706 AN: 33466

American (AMR) AF: 0.139 AC: 6220 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.204 AC: 5332 AN: 26108

East Asian (EAS) AF: 0.0467 AC: 1855 AN: 39698

South Asian (SAS) AF: 0.200 AC: 17273 AN: 86236

European-Finnish (FIN) AF: 0.0665 AC: 3547 AN: 53356

Middle Eastern (MID) AF: 0.265 AC: 1517 AN: 5726

European-Non Finnish (NFE) AF: 0.165 AC: 183547 AN: 1111854

Other (OTH) AF: 0.177 AC: 10705 AN: 60378

GnomAD4 genome AF: 0.161 AC: 24525 AN: 152208 Hom.: 2231 Cov.: 32 AF XY: 0.158 AC XY: 11793 AN XY: 74428

African (AFR) AF: 0.194 AC: 8049 AN: 41516

American (AMR) AF: 0.164 AC: 2515 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.195 AC: 677 AN: 3470

East Asian (EAS) AF: 0.0493 AC: 255 AN: 5172

South Asian (SAS) AF: 0.207 AC: 1000 AN: 4826

European-Finnish (FIN) AF: 0.0573 AC: 608 AN: 10614

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.159 AC: 10779 AN: 68002

Other (OTH) AF: 0.196 AC: 413 AN: 2112

Alfa AF: 0.160 Hom.: 2799

Bravo AF: 0.171

Asia WGS AF: 0.109 AC: 381 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Neuronopathy, distal hereditary motor, autosomal recessive 5 (2)
-	-	1	Charcot-Marie-Tooth disease (1)
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	7.4
DANN	Benign	0.71
PhyloP100		0.46
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3731897; hg19: chr2-220146651; COSMIC: COSV60675579; COSMIC: COSV60675579;