2-197487080-CCACCCATTG-CCACCCATTGCACCCATTG

Variant names:

• chr2-197487080-C-CCACCCATTG
• rs1347832996
• NM_002156.5:c.1679_1687dupCAATGGGTG

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PM4

The NM_002156.5(HSPD1):​c.1679_1687dupCAATGGGTG​(p.Ala560_Gly562dup) variant causes a conservative inframe insertion change. The variant allele was found at a frequency of 0.000000727 in 1,375,082 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: HSPD1 NM_002156.5 conservative_inframe_insertion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.98
• 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_002156.5.

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.1679_1687dupCAATGGGTG	p.Ala560_Gly562dup	conservative_inframe_insertion	Exon 12 of 12	NP_002147.2
	HSPD1	NM_199440.2		c.1679_1687dupCAATGGGTG	p.Ala560_Gly562dup	conservative_inframe_insertion	Exon 12 of 12	NP_955472.1	A0A024R3X4
	SNORA105B	NR_132788.1		n.-186_-178dupCAATGGGTG		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.1679_1687dupCAATGGGTG	p.Ala560_Gly562dup	conservative_inframe_insertion	Exon 12 of 12	ENSP00000373620.3	P10809-1
	HSPD1	ENST00000954440.1		c.1727_1735dupCAATGGGTG	p.Ala576_Gly578dup	conservative_inframe_insertion	Exon 12 of 12	ENSP00000624499.1
	HSPD1	ENST00000345042.6	TSL:5	c.1679_1687dupCAATGGGTG	p.Ala560_Gly562dup	conservative_inframe_insertion	Exon 12 of 12	ENSP00000340019.2	P10809-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.27e-7 AC: 1 AN: 1375082 Hom.: 0 Cov.: 21 AF XY: 0.00000145 AC XY: 1 AN XY: 689084

African (AFR) AF: 0.00 AC: 0 AN: 31648

American (AMR) AF: 0.00 AC: 0 AN: 44550

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25608

East Asian (EAS) AF: 0.00 AC: 0 AN: 39300

South Asian (SAS) AF: 0.0000118 AC: 1 AN: 84570

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53372

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5590

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1032974

Other (OTH) AF: 0.00 AC: 0 AN: 57470

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.0
Mutation Taster		=52/48	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs1347832996; hg19: chr2-198351804;