rs2605039

Variant names:

• chr2-197498127-C-A
• rs2605039
• NM_002156.5:c.174+548G>T

Your query was ambiguous. Multiple possible variants found:

• chr2-197498127-C-A
• chr2-197498127-C-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.174+548G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.706 in 152,118 control chromosomes in the GnomAD database, including 38,677 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 (38677 hom., cov: 33)
• Consequence: HSPD1 NM_002156.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.898
• Publications: 16 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.829 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSPD1	NM_002156.5	c.174+548G>T		intron_variant	Intron 2 of 11	ENST00000388968.8	NP_002147.2
HSPD1	NM_199440.2	c.174+548G>T		intron_variant	Intron 2 of 11		NP_955472.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HSPD1	ENST00000388968.8	c.174+548G>T		intron_variant	Intron 2 of 11	1	NM_002156.5	ENSP00000373620.3

Frequencies

GnomAD3 genomes AF: 0.706 AC: 107323 AN: 152000 Hom.: 38639 Cov.: 33

Gnomad AFR AF: 0.836

Gnomad AMI AF: 0.713

Gnomad AMR AF: 0.649

Gnomad ASJ AF: 0.748

Gnomad EAS AF: 0.508

Gnomad SAS AF: 0.692

Gnomad FIN AF: 0.571

Gnomad MID AF: 0.861

Gnomad NFE AF: 0.673

Gnomad OTH AF: 0.725

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

GnomAD4 genome AF: 0.706 AC: 107415 AN: 152118 Hom.: 38677 Cov.: 33 AF XY: 0.702 AC XY: 52188 AN XY: 74364

African (AFR) AF: 0.836 AC: 34707 AN: 41516

American (AMR) AF: 0.649 AC: 9908 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.748 AC: 2595 AN: 3470

East Asian (EAS) AF: 0.509 AC: 2630 AN: 5166

South Asian (SAS) AF: 0.693 AC: 3343 AN: 4826

European-Finnish (FIN) AF: 0.571 AC: 6026 AN: 10562

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

European-Non Finnish (NFE) AF: 0.673 AC: 45775 AN: 67988

Other (OTH) AF: 0.724 AC: 1528 AN: 2110

Alfa AF: 0.688 Hom.: 5515

Bravo AF: 0.716

Asia WGS AF: 0.615 AC: 2142 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.71
DANN	Benign	0.29
PhyloP100		-0.90
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: rs2605039; hg19: chr2-198362851;