chr2-197497294-T-C

Variant names:

Variant summary

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

The NM_002156.5(HSPD1):c.273A>G(p.Lys91Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.666 in 1,612,620 control chromosomes in the GnomAD database, including 360,608 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.67 ( 34541 hom., cov: 33)

Exomes 𝑓: 0.67 ( 326067 hom. )

Consequence

HSPD1
NM_002156.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: 0.897

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:

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=-0.64).

BP6

Variant 2-197497294-T-C is Benign according to our data. Variant chr2-197497294-T-C is described in ClinVar as [Benign]. Clinvar id is 129241.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-197497294-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.897 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.71 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSPD1	NM_002156.5 link	c.273A>G	p.Lys91Lys	synonymous_variant	Exon 3 of 12	ENST00000388968.8	NP_002147.2	P10809-1A0A024R3X4
HSPD1	NM_199440.2 link	c.273A>G	p.Lys91Lys	synonymous_variant	Exon 3 of 12		NP_955472.1	P10809-1A0A024R3X4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HSPD1	ENST00000388968.8 link	c.273A>G	p.Lys91Lys	synonymous_variant	Exon 3 of 12	1	NM_002156.5	ENSP00000373620.3		P10809-1

Frequencies

GnomAD3 genomes

AF:

0.671

AC:

101969

AN:

151992

Hom.:

34518

Cov.:

show subpopulations

Gnomad AFR

AF:

0.717

Gnomad AMI

AF:

0.714

Gnomad AMR

AF:

0.637

Gnomad ASJ

AF:

0.744

Gnomad EAS

AF:

0.503

Gnomad SAS

AF:

0.683

Gnomad FIN

AF:

0.571

Gnomad MID

AF:

0.848

Gnomad NFE

AF:

0.672

Gnomad OTH

AF:

0.697

GnomAD3 exomes

AF:

0.639

AC:

160735

AN:

251372

Hom.:

52667

AF XY:

0.651

AC XY:

88457

AN XY:

135864

show subpopulations

Gnomad AFR exome

AF:

0.715

Gnomad AMR exome

AF:

0.490

Gnomad ASJ exome

AF:

0.747

Gnomad EAS exome

AF:

0.512

Gnomad SAS exome

AF:

0.695

Gnomad FIN exome

AF:

0.577

Gnomad NFE exome

AF:

0.680

Gnomad OTH exome

AF:

0.688

GnomAD4 exome

AF:

0.666

AC:

972323

AN:

1460510

Hom.:

326067

Cov.:

AF XY:

0.668

AC XY:

485304

AN XY:

726628

show subpopulations

Gnomad4 AFR exome

AF:

0.723

Gnomad4 AMR exome

AF:

0.512

Gnomad4 ASJ exome

AF:

0.743

Gnomad4 EAS exome

AF:

0.555

Gnomad4 SAS exome

AF:

0.696

Gnomad4 FIN exome

AF:

0.579

Gnomad4 NFE exome

AF:

0.673

Gnomad4 OTH exome

AF:

0.669

GnomAD4 genome

AF:

0.671

AC:

102040

AN:

152110

Hom.:

34541

Cov.:

AF XY:

0.668

AC XY:

49640

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.717

Gnomad4 AMR

AF:

0.636

Gnomad4 ASJ

AF:

0.744

Gnomad4 EAS

AF:

0.504

Gnomad4 SAS

AF:

0.684

Gnomad4 FIN

AF:

0.571

Gnomad4 NFE

AF:

0.672

Gnomad4 OTH

AF:

0.694

Alfa

AF:

0.679

Hom.:

15140

Bravo

AF:

0.676

Asia WGS

AF:

0.591

AC:

2060

AN:

3478

EpiCase

AF:

0.706

EpiControl

AF:

0.707

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Sep 05, 2013

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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. -

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: 65% of total chromosomes in ExAC -

Hereditary spastic paraplegia 13

Benign:2

Aug 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Spastic paraplegia

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Hypomyelinating leukodystrophy 4

Benign:1

Aug 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Hereditary spastic paraplegia

Benign:1

Dec 12, 2016

Genome Diagnostics Laboratory, The Hospital for Sick Children

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

8.8

DANN

Benign

0.88

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