2-197498780-A-G

Position:

chr2-197498780-A-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_002156.5(HSPD1):c.69T>C(p.Thr23Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 1,609,464 control chromosomes in the GnomAD database, including 24,827 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 2307 hom., cov: 33)

Exomes 𝑓: 0.18 ( 22520 hom. )

Consequence

HSPD1
NM_002156.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.182

Variant links:

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]

HSPD1 links:

HSPD1 (HGNC:):

HSPD1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BP6

Variant 2-197498780-A-G is Benign according to our data. Variant chr2-197498780-A-G is described in ClinVar as [Benign]. Clinvar id is 129243.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-197498780-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.182 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.229 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HSPD1	NM_002156.5 linkuse as main transcript	c.69T>C	p.Thr23Thr	synonymous_variant	2/12	ENST00000388968.8	NP_002147.2	P10809-1A0A024R3X4
HSPD1	NM_199440.2 linkuse as main transcript	c.69T>C	p.Thr23Thr	synonymous_variant	2/12		NP_955472.1	P10809-1A0A024R3X4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HSPD1	ENST00000388968.8 linkuse as main transcript	c.69T>C	p.Thr23Thr	synonymous_variant	2/12	1	NM_002156.5	ENSP00000373620.3		P10809-1

Frequencies

GnomAD3 genomes

AF:

0.168

AC:

25580

AN:

152092

Hom.:

2304

Cov.:

show subpopulations

Gnomad AFR

AF:

0.110

Gnomad AMI

AF:

0.196

Gnomad AMR

AF:

0.197

Gnomad ASJ

AF:

0.235

Gnomad EAS

AF:

0.239

Gnomad SAS

AF:

0.117

Gnomad FIN

AF:

0.184

Gnomad MID

AF:

0.278

Gnomad NFE

AF:

0.188

Gnomad OTH

AF:

0.195

GnomAD3 exomes

AF:

0.173

AC:

43350

AN:

250876

Hom.:

2540

AF XY:

0.172

AC XY:

23309

AN XY:

135586

show subpopulations

Gnomad AFR exome

AF:

0.105

Gnomad AMR exome

AF:

0.185

Gnomad ASJ exome

AF:

0.219

Gnomad EAS exome

AF:

0.230

Gnomad SAS exome

AF:

0.113

Gnomad FIN exome

AF:

0.178

Gnomad NFE exome

AF:

0.179

Gnomad OTH exome

AF:

0.202

GnomAD4 exome

AF:

0.182

AC:

265548

AN:

1457254

Hom.:

22520

Cov.:

AF XY:

0.181

AC XY:

131249

AN XY:

725130

show subpopulations

Gnomad4 AFR exome

AF:

0.106

Gnomad4 AMR exome

AF:

0.191

Gnomad4 ASJ exome

AF:

0.232

Gnomad4 EAS exome

AF:

0.233

Gnomad4 SAS exome

AF:

0.117

Gnomad4 FIN exome

AF:

0.184

Gnomad4 NFE exome

AF:

0.186

Gnomad4 OTH exome

AF:

0.184

GnomAD4 genome

AF:

0.168

AC:

25611

AN:

152210

Hom.:

2307

Cov.:

AF XY:

0.169

AC XY:

12581

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.110

Gnomad4 AMR

AF:

0.197

Gnomad4 ASJ

AF:

0.235

Gnomad4 EAS

AF:

0.240

Gnomad4 SAS

AF:

0.118

Gnomad4 FIN

AF:

0.184

Gnomad4 NFE

AF:

0.188

Gnomad4 OTH

AF:

0.197

Alfa

AF:

0.175

Hom.:

916

Bravo

AF:

0.170

Asia WGS

AF:

0.176

AC:

611

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 25, 2013	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

Spastic paraplegia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Hereditary spastic paraplegia 13

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Hereditary spastic paraplegia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Dec 12, 2016

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Benign

0.81

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over