2-197497800-C-T

Variant names:

• chr2-197497800-C-T
• rs17730989
• NM_002156.5:c.175-408G>A

Variant summary

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

The NM_002156.5(HSPD1):​c.175-408G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.42 in 152,064 control chromosomes in the GnomAD database, including 13,971 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 0.42 (13971 hom., cov: 33)
• Consequence: HSPD1 NM_002156.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.13
• Publications: 10 publications found

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 Gene-Disease associations (from GenCC):

• hereditary spastic paraplegia 13

  Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• hypomyelinating leukodystrophy 4

  Inheritance: AR Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet, Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.54 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002156.5. 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
	HSPD1	NM_002156.5	MANE Select	c.175-408G>A		intron	N/A	NP_002147.2
	HSPD1	NM_199440.2		c.175-408G>A		intron	N/A	NP_955472.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSPD1	ENST00000388968.8	TSL:1 MANE Select	c.175-408G>A		intron	N/A	ENSP00000373620.3
	HSPD1	ENST00000345042.6	TSL:5	c.175-408G>A		intron	N/A	ENSP00000340019.2
	HSPD1	ENST00000418022.2	TSL:4	c.175-408G>A		intron	N/A	ENSP00000412227.2

Frequencies

GnomAD3 genomes AF: 0.420 AC: 63821 AN: 151946 Hom.: 13980 Cov.: 33

Gnomad AFR AF: 0.323

Gnomad AMI AF: 0.518

Gnomad AMR AF: 0.406

Gnomad ASJ AF: 0.508

Gnomad EAS AF: 0.264

Gnomad SAS AF: 0.559

Gnomad FIN AF: 0.385

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.483

Gnomad OTH AF: 0.438

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.420 AC: 63809 AN: 152064 Hom.: 13971 Cov.: 33 AF XY: 0.418 AC XY: 31078 AN XY: 74310

African (AFR) AF: 0.322 AC: 13366 AN: 41470

American (AMR) AF: 0.406 AC: 6205 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.508 AC: 1761 AN: 3468

East Asian (EAS) AF: 0.264 AC: 1366 AN: 5174

South Asian (SAS) AF: 0.558 AC: 2693 AN: 4826

European-Finnish (FIN) AF: 0.385 AC: 4064 AN: 10544

Middle Eastern (MID) AF: 0.551 AC: 162 AN: 294

European-Non Finnish (NFE) AF: 0.483 AC: 32804 AN: 67980

Other (OTH) AF: 0.434 AC: 917 AN: 2114

Alfa AF: 0.467 Hom.: 21466

Bravo AF: 0.410

Asia WGS AF: 0.391 AC: 1364 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.2
DANN	Benign	0.41
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: rs17730989; hg19: chr2-198362524;