chr5-34929825-G-A

Variant names:

• chr5-34929825-G-A
• rs762491366
• NM_001012339.3:c.6G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_001012339.3(DNAJC21):​c.6G>A​(p.Lys2Lys) variant causes a synonymous change. The variant allele was found at a frequency of 0.00000918 in 1,525,038 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 0.000040 (0 hom., cov: 29)
  • Exomes 𝑓: 0.0000058 (0 hom.)
• Consequence: DNAJC21 NM_001012339.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.16
• Publications: 0 publications found

Genes affected

DNAJC21 (HGNC:27030): (DnaJ heat shock protein family (Hsp40) member C21) This gene encodes a member of the DNAJ heat shock protein 40 family of proteins that is characterized by two N-terminal tetratricopeptide repeat domains and a C-terminal DNAJ domain. This protein binds the precursor 45S ribosomal RNA and may be involved in early nuclear ribosomal RNA biogenesis and maturation of the 60S ribosomal subunit. Mutations in this gene result in Bone marrow failure syndrome 3. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Feb 2017]

DNAJC21 Gene-Disease associations (from GenCC):

• bone marrow failure syndrome 3

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• Shwachman-Diamond syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000302970 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP6: Variant 5-34929825-G-A is Benign according to our data. Variant chr5-34929825-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2882549.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAJC21	NM_001012339.3	c.6G>A	p.Lys2Lys	synonymous_variant	Exon 1 of 12	ENST00000648817.1	NP_001012339.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAJC21	ENST00000648817.1	c.6G>A	p.Lys2Lys	synonymous_variant	Exon 1 of 12		NM_001012339.3	ENSP00000497410.1

Frequencies

GnomAD3 genomes AF: 0.0000399 AC: 6 AN: 150390 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.00

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: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000890

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000516 AC: 1 AN: 193698 AF XY: 0.00000927

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000114

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000582 AC: 8 AN: 1374648 Hom.: 0 Cov.: 31 AF XY: 0.00000731 AC XY: 5 AN XY: 684254

African (AFR) AF: 0.00 AC: 0 AN: 28504

American (AMR) AF: 0.00 AC: 0 AN: 37012

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23546

East Asian (EAS) AF: 0.00 AC: 0 AN: 31642

South Asian (SAS) AF: 0.00 AC: 0 AN: 79170

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49510

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4776

European-Non Finnish (NFE) AF: 0.00000751 AC: 8 AN: 1065212

Other (OTH) AF: 0.00 AC: 0 AN: 55276

GnomAD4 genome AF: 0.0000399 AC: 6 AN: 150390 Hom.: 0 Cov.: 29 AF XY: 0.0000409 AC XY: 3 AN XY: 73408

African (AFR) AF: 0.00 AC: 0 AN: 41182

American (AMR) AF: 0.00 AC: 0 AN: 15146

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3458

East Asian (EAS) AF: 0.00 AC: 0 AN: 5074

South Asian (SAS) AF: 0.00 AC: 0 AN: 4804

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10042

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000890 AC: 6 AN: 67398

Other (OTH) AF: 0.00 AC: 0 AN: 2064

Alfa AF: 0.0000388 Hom.: 0

Bravo AF: 0.0000113

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Sep 09, 2023

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	15
DANN	Benign	0.97
PhyloP100		4.2
PromoterAI		0.0090	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs762491366; hg19: chr5-34929930;