2-197498127-C-A

Position:

• chr2-197498127-C-A

Variant summary

Our verdict is Benign. Variant got -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

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
HSPD1	NM_002156.5	c.174+548G>T		intron_variant		ENST00000388968.8	NP_002147.2
HSPD1	NM_199440.2	c.174+548G>T		intron_variant			NP_955472.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HSPD1	ENST00000388968.8	c.174+548G>T		intron_variant		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

Gnomad4 AFR AF: 0.836

Gnomad4 AMR AF: 0.649

Gnomad4 ASJ AF: 0.748

Gnomad4 EAS AF: 0.509

Gnomad4 SAS AF: 0.693

Gnomad4 FIN AF: 0.571

Gnomad4 NFE AF: 0.673

Gnomad4 OTH AF: 0.724

Alfa AF: 0.684 Hom.: 5261

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

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

Other links and lift over

dbSNP: rs2605039; hg19: chr2-198362851;