rs2306819

Variant names:

• chr11-73970045-C-T
• rs2306819
• NM_153614.4:c.882C>T
• DNAJB13 p.Phe294Phe

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_153614.4(DNAJB13):​c.882C>T​(p.Phe294Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.289 in 1,609,274 control chromosomes in the GnomAD database, including 68,644 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.28 (6202 hom., cov: 32)
  • Exomes 𝑓: 0.29 (62442 hom.)
• Consequence: DNAJB13 NM_153614.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -1.10
• Publications: 21 publications found

Genes affected

DNAJB13 (HGNC:30718): (DnaJ heat shock protein family (Hsp40) member B13) This gene encodes a member of the heat shock protein 40 co-chaperone family which is produced in large amounts in the testis and is located on the radial spokes of the axoneme in human sperm flagella and other flagellar structures. The encoded protein associates with the sperm annulus, as part of the septin complex, through direct interaction with septin 4, during sperm terminal differentiation. Naturally occurring mutations in this gene are associated with primary ciliary dyskinesia and male infertility. [provided by RefSeq, Apr 2017]

DNAJB13 Gene-Disease associations (from GenCC):

• primary ciliary dyskinesia 34

  Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: Ambry Genetics, G2P, ClinGen, Labcorp Genetics (formerly Invitae)
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP6: Variant 11-73970045-C-T is Benign according to our data. Variant chr11-73970045-C-T is described in ClinVar as Benign. ClinVar VariationId is 1253105.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.1 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.351 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153614.4. 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
	DNAJB13	NM_153614.4	MANE Select	c.882C>T	p.Phe294Phe	synonymous	Exon 8 of 8	NP_705842.2
	DNAJB13	NM_001441321.1		c.720C>T	p.Phe240Phe	synonymous	Exon 7 of 7	NP_001428250.1
	DNAJB13	NM_001377263.1		c.708C>T	p.Phe236Phe	synonymous	Exon 9 of 9	NP_001364192.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAJB13	ENST00000339764.6	TSL:1 MANE Select	c.882C>T	p.Phe294Phe	synonymous	Exon 8 of 8	ENSP00000344431.1	P59910-1
	DNAJB13	ENST00000543947.1	TSL:1	c.357C>T	p.Phe119Phe	synonymous	Exon 5 of 6	ENSP00000438576.1	P59910-2
	DNAJB13	ENST00000897971.1		c.720C>T	p.Phe240Phe	synonymous	Exon 7 of 7	ENSP00000568030.1

Frequencies

GnomAD3 genomes AF: 0.279 AC: 42433 AN: 151876 Hom.: 6205 Cov.: 32

Gnomad AFR AF: 0.219

Gnomad AMI AF: 0.374

Gnomad AMR AF: 0.358

Gnomad ASJ AF: 0.294

Gnomad EAS AF: 0.151

Gnomad SAS AF: 0.216

Gnomad FIN AF: 0.310

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.305

Gnomad OTH AF: 0.309

GnomAD2 exomes AF: 0.285 AC: 69953 AN: 245486 AF XY: 0.282

Gnomad AFR exome AF: 0.218

Gnomad AMR exome AF: 0.367

Gnomad ASJ exome AF: 0.292

Gnomad EAS exome AF: 0.129

Gnomad FIN exome AF: 0.303

Gnomad NFE exome AF: 0.307

Gnomad OTH exome AF: 0.304

GnomAD4 exome AF: 0.290 AC: 422136 AN: 1457280 Hom.: 62442 Cov.: 35 AF XY: 0.288 AC XY: 208524 AN XY: 724702

African (AFR) AF: 0.214 AC: 7150 AN: 33396

American (AMR) AF: 0.370 AC: 16273 AN: 44030

Ashkenazi Jewish (ASJ) AF: 0.296 AC: 7697 AN: 26036

East Asian (EAS) AF: 0.177 AC: 7002 AN: 39566

South Asian (SAS) AF: 0.228 AC: 19395 AN: 85142

European-Finnish (FIN) AF: 0.305 AC: 16251 AN: 53360

Middle Eastern (MID) AF: 0.328 AC: 1883 AN: 5746

European-Non Finnish (NFE) AF: 0.297 AC: 329638 AN: 1109766

Other (OTH) AF: 0.280 AC: 16847 AN: 60238

GnomAD4 genome AF: 0.279 AC: 42443 AN: 151994 Hom.: 6202 Cov.: 32 AF XY: 0.279 AC XY: 20689 AN XY: 74278

African (AFR) AF: 0.218 AC: 9055 AN: 41466

American (AMR) AF: 0.359 AC: 5472 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.294 AC: 1018 AN: 3466

East Asian (EAS) AF: 0.151 AC: 781 AN: 5176

South Asian (SAS) AF: 0.215 AC: 1037 AN: 4814

European-Finnish (FIN) AF: 0.310 AC: 3267 AN: 10546

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.305 AC: 20727 AN: 67958

Other (OTH) AF: 0.305 AC: 642 AN: 2106

Alfa AF: 0.300 Hom.: 11665

Bravo AF: 0.283

Asia WGS AF: 0.191 AC: 664 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	4.3
DANN	Benign	0.84
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2306819;

hg19: chr11-73681090;

COSMIC: COSV60104595;

COSMIC: COSV60104595;