2-197487067-A-ACCACCTCCCATT

Variant names:

• chr2-197487066-TA-TACCACCTCCCAT
• NM_002156.5:c.1690_1700dupATGGGAGGTGG

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PVS1_Moderate

The NM_002156.5(HSPD1):​c.1690_1700dupATGGGAGGTGG​(p.Met568TrpfsTer13) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. G567G) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: HSPD1 NM_002156.5 frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.21
• Publications: 0 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]

SNORA105B (HGNC:51398): (small nucleolar RNA, H/ACA box 105B)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.0128 CDS is truncated, and there are 0 pathogenic variants in the truncated region.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSPD1	NM_002156.5	MANE Select	c.1690_1700dupATGGGAGGTGG	p.Met568TrpfsTer13	frameshift	Exon 12 of 12	NP_002147.2
	HSPD1	NM_199440.2		c.1690_1700dupATGGGAGGTGG	p.Met568TrpfsTer13	frameshift	Exon 12 of 12	NP_955472.1	A0A024R3X4
	SNORA105B	NR_132788.1		n.-175_-165dupATGGGAGGTGG		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSPD1	ENST00000388968.8	TSL:1 MANE Select	c.1690_1700dupATGGGAGGTGG	p.Met568TrpfsTer13	frameshift	Exon 12 of 12	ENSP00000373620.3	P10809-1
	HSPD1	ENST00000954440.1		c.1738_1748dupATGGGAGGTGG	p.Met584TrpfsTer13	frameshift	Exon 12 of 12	ENSP00000624499.1
	HSPD1	ENST00000345042.6	TSL:5	c.1690_1700dupATGGGAGGTGG	p.Met568TrpfsTer13	frameshift	Exon 12 of 12	ENSP00000340019.2	P10809-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 21

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		5.2

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr2-198351790;