2-24946331-A-G

Position:

• chr2-24946331-A-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAJC27	NM_016544.3	c.*1285T>C		3_prime_UTR_variant	7/7	ENST00000264711.7	NP_057628.1
DNAJC27	NM_001198559.1	c.*1412T>C		3_prime_UTR_variant	6/6		NP_001185488.1
DNAJC27	XM_047444647.1	c.*1285T>C		3_prime_UTR_variant	7/7		XP_047300603.1
DNAJC27	XM_047444648.1	c.*1285T>C		3_prime_UTR_variant	7/7		XP_047300604.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAJC27	ENST00000264711	c.*1285T>C		3_prime_UTR_variant	7/7	1	NM_016544.3	ENSP00000264711.2
DNAJC27	ENST00000534855	c.*1412T>C		3_prime_UTR_variant	6/6	1		ENSP00000440086.2

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

Gnomad4 AFR exome AF: 1.00

Gnomad4 AMR exome AF: 0.500

Gnomad4 EAS exome AF: 0.500

Gnomad4 SAS exome AF: 0.500

Gnomad4 NFE exome AF: 0.525

Gnomad4 OTH exome AF: 0.667

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

Gnomad4 AFR AF: 0.875

Gnomad4 AMR AF: 0.412

Gnomad4 ASJ AF: 0.411

Gnomad4 EAS AF: 0.484

Gnomad4 SAS AF: 0.489

Gnomad4 FIN AF: 0.384

Gnomad4 NFE AF: 0.474

Gnomad4 OTH AF: 0.523

Alfa AF: 0.484 Hom.: 30444

Bravo AF: 0.586

Asia WGS AF: 0.469 AC: 1633 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	9.0
DANN	Benign	0.85

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

Publications

LitVar

Other links and lift over

dbSNP: rs1172294; hg19: chr2-25169200;