2-24946331-A-G

Variant names:

• chr2-24946331-A-G
• rs1172294
• NM_016544.3:c.*1285T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016544.3(DNAJC27):​c.*1285T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.571 in 152,234 control chromosomes in the GnomAD database, including 27,775 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.57 (27770 hom., cov: 33)
  • Exomes 𝑓: 0.55 (5 hom.)
• Consequence: DNAJC27 NM_016544.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.08
• Publications: 36 publications found

Genes affected

DNAJC27 (HGNC:30290): (DnaJ heat shock protein family (Hsp40) member C27) Predicted to enable GTPase activity. Predicted to be involved in intracellular protein transport and positive regulation of MAPK cascade. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000309511 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.868 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016544.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAJC27	NM_016544.3	MANE Select	c.*1285T>C		3_prime_UTR	Exon 7 of 7	NP_057628.1
	DNAJC27	NM_001198559.1		c.*1412T>C		3_prime_UTR	Exon 6 of 6	NP_001185488.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAJC27	ENST00000264711.7	TSL:1 MANE Select	c.*1285T>C		3_prime_UTR	Exon 7 of 7	ENSP00000264711.2
	DNAJC27	ENST00000534855.5	TSL:1	c.*1412T>C		3_prime_UTR	Exon 6 of 6	ENSP00000440086.2
	ENSG00000309511	ENST00000841804.1		n.190-1303A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.571 AC: 86793 AN: 152060 Hom.: 27704 Cov.: 33

Gnomad AFR AF: 0.875

Gnomad AMI AF: 0.452

Gnomad AMR AF: 0.413

Gnomad ASJ AF: 0.411

Gnomad EAS AF: 0.484

Gnomad SAS AF: 0.487

Gnomad FIN AF: 0.384

Gnomad MID AF: 0.398

Gnomad NFE AF: 0.474

Gnomad OTH AF: 0.529

GnomAD4 exome AF: 0.554 AC: 31 AN: 56 Hom.: 5 Cov.: 0 AF XY: 0.558 AC XY: 29 AN XY: 52

African (AFR) AF: 1.00 AC: 2 AN: 2

American (AMR) AF: 0.500 AC: 1 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.500 AC: 1 AN: 2

South Asian (SAS) AF: 0.500 AC: 2 AN: 4

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.525 AC: 21 AN: 40

Other (OTH) AF: 0.667 AC: 4 AN: 6

GnomAD4 genome AF: 0.571 AC: 86903 AN: 152178 Hom.: 27770 Cov.: 33 AF XY: 0.560 AC XY: 41647 AN XY: 74390

African (AFR) AF: 0.875 AC: 36356 AN: 41538

American (AMR) AF: 0.412 AC: 6306 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.411 AC: 1426 AN: 3470

East Asian (EAS) AF: 0.484 AC: 2505 AN: 5172

South Asian (SAS) AF: 0.489 AC: 2362 AN: 4828

European-Finnish (FIN) AF: 0.384 AC: 4068 AN: 10586

Middle Eastern (MID) AF: 0.390 AC: 114 AN: 292

European-Non Finnish (NFE) AF: 0.474 AC: 32253 AN: 67986

Other (OTH) AF: 0.523 AC: 1102 AN: 2108

Alfa AF: 0.503 Hom.: 80198

Bravo AF: 0.586

Asia WGS AF: 0.469 AC: 1633 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	9.0
DANN	Benign	0.85
PhyloP100		1.1
Mutation Taster		=100/0	polymorphism (auto)

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: rs1172294; hg19: chr2-25169200;