2-197489690-T-C

Variant names:

• chr2-197489690-T-C
• rs2565163
• NM_002156.5:c.970-443A>G

Variant summary

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

The NM_002156.5(HSPD1):​c.970-443A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.709 in 151,890 control chromosomes in the GnomAD database, including 38,991 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 0.71 (38991 hom., cov: 30)
• Consequence: HSPD1 NM_002156.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.73
• 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.838 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSPD1	NM_002156.5	c.970-443A>G		intron_variant	Intron 8 of 11	ENST00000388968.8	NP_002147.2
HSPD1	NM_199440.2	c.970-443A>G		intron_variant	Intron 8 of 11		NP_955472.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HSPD1	ENST00000388968.8	c.970-443A>G		intron_variant	Intron 8 of 11	1	NM_002156.5	ENSP00000373620.3

Frequencies

GnomAD3 genomes AF: 0.709 AC: 107627 AN: 151772 Hom.: 38953 Cov.: 30

Gnomad AFR AF: 0.845

Gnomad AMI AF: 0.714

Gnomad AMR AF: 0.650

Gnomad ASJ AF: 0.747

Gnomad EAS AF: 0.507

Gnomad SAS AF: 0.697

Gnomad FIN AF: 0.571

Gnomad MID AF: 0.861

Gnomad NFE AF: 0.674

Gnomad OTH AF: 0.728

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

GnomAD4 genome AF: 0.709 AC: 107720 AN: 151890 Hom.: 38991 Cov.: 30 AF XY: 0.705 AC XY: 52313 AN XY: 74220

African (AFR) AF: 0.845 AC: 35041 AN: 41448

American (AMR) AF: 0.649 AC: 9896 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.747 AC: 2589 AN: 3464

East Asian (EAS) AF: 0.508 AC: 2616 AN: 5148

South Asian (SAS) AF: 0.698 AC: 3354 AN: 4808

European-Finnish (FIN) AF: 0.571 AC: 6024 AN: 10546

Middle Eastern (MID) AF: 0.864 AC: 254 AN: 294

European-Non Finnish (NFE) AF: 0.674 AC: 45763 AN: 67922

Other (OTH) AF: 0.727 AC: 1532 AN: 2106

Alfa AF: 0.696 Hom.: 46669

Bravo AF: 0.719

Asia WGS AF: 0.617 AC: 2151 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.93
DANN	Benign	0.16
PhyloP100		-1.7
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: rs2565163; hg19: chr2-198354414;