rs3214832

Positions:

• chr2-197494591-CAGATAACTCAAACTTTTGATCATA-C
• chr2-197494591-CAGATAACTCAAACTTTTGATCATA-CAGATAACTCAAACTTTTGATCATAAGATAACTCAAACTTTTGATCATA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_002156.5(HSPD1):​c.606+42_606+65del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 1,153,152 control chromosomes in the GnomAD database, including 20,383 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.17 (2262 hom., cov: 29)
  • Exomes 𝑓: 0.20 (18121 hom.)
• Consequence: HSPD1 NM_002156.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.01

Genes affected

HSPD1 (HGNC:5261): (heat shock protein family D (Hsp60) member 1) This gene encodes a member of the chaperonin family. The encoded mitochondrial protein may function as a signaling molecule in the innate immune system. This protein is essential for the folding and assembly of newly imported proteins in the mitochondria. This gene is adjacent to a related family member and the region between the 2 genes functions as a bidirectional promoter. Several pseudogenes have been associated with this gene. Two transcript variants encoding the same protein have been identified for this gene. Mutations associated with this gene cause autosomal recessive spastic paraplegia 13. [provided by RefSeq, Jun 2010]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 2-197494591-CAGATAACTCAAACTTTTGATCATA-C is Benign according to our data. Variant chr2-197494591-CAGATAACTCAAACTTTTGATCATA-C is described in ClinVar as [Benign]. Clinvar id is 1259574.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.227 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HSPD1	NM_002156.5	c.606+42_606+65del		intron_variant		ENST00000388968.8	NP_002147.2
HSPD1	NM_199440.2	c.606+42_606+65del		intron_variant			NP_955472.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HSPD1	ENST00000388968.8	c.606+42_606+65del		intron_variant		1	NM_002156.5	ENSP00000373620	P1

Frequencies

GnomAD3 genomes AF: 0.167 AC: 25421 AN: 151928 Hom.: 2259 Cov.: 29

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.193

Gnomad AMR AF: 0.197

Gnomad ASJ AF: 0.234

Gnomad EAS AF: 0.237

Gnomad SAS AF: 0.116

Gnomad FIN AF: 0.183

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.187

Gnomad OTH AF: 0.194

GnomAD4 exome AF: 0.204 AC: 203885 AN: 1001106 Hom.: 18121 AF XY: 0.200 AC XY: 103537 AN XY: 517282

Gnomad4 AFR exome AF: 0.120

Gnomad4 AMR exome AF: 0.198

Gnomad4 ASJ exome AF: 0.241

Gnomad4 EAS exome AF: 0.239

Gnomad4 SAS exome AF: 0.124

Gnomad4 FIN exome AF: 0.186

Gnomad4 NFE exome AF: 0.214

Gnomad4 OTH exome AF: 0.199

GnomAD4 genome AF: 0.167 AC: 25452 AN: 152046 Hom.: 2262 Cov.: 29 AF XY: 0.168 AC XY: 12502 AN XY: 74338

Gnomad4 AFR AF: 0.109

Gnomad4 AMR AF: 0.196

Gnomad4 ASJ AF: 0.234

Gnomad4 EAS AF: 0.238

Gnomad4 SAS AF: 0.117

Gnomad4 FIN AF: 0.183

Gnomad4 NFE AF: 0.187

Gnomad4 OTH AF: 0.196

Alfa AF: 0.167 Hom.: 222

Asia WGS AF: 0.176 AC: 610 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 29, 2018

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3214832; hg19: chr2-198359315;