chr2-197500319-C-G

Position:

• chr2-197500319-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000409729.1(HSPE1):​c.-118C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.673 in 1,497,840 control chromosomes in the GnomAD database, including 340,952 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.68 (35878 hom., cov: 33)
  • Exomes 𝑓: 0.67 (305074 hom.)
• Consequence: HSPE1 ENST00000409729.1 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.160

Genes affected

HSPE1 (HGNC:5269): (heat shock protein family E (Hsp10) member 1) This gene encodes a major heat shock protein which functions as a chaperonin. Its structure consists of a heptameric ring which binds to another heat shock protein in order to form a symmetric, functional heterodimer which enhances protein folding in an ATP-dependent manner. This gene and its co-chaperonin, HSPD1, are arranged in a head-to-head orientation on chromosome 2. Naturally occurring read-through transcription occurs between this locus and the neighboring locus MOBKL3.[provided by RefSeq, Feb 2011]

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 2-197500319-C-G is Benign according to our data. Variant chr2-197500319-C-G is described in ClinVar as [Benign]. Clinvar id is 1271798.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.748 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.197500319C>G		intergenic_region
HSPD1	NM_199440.2	c.-162G>C		upstream_gene_variant			NP_955472.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HSPE1	ENST00000409729.1	c.-118C>G		5_prime_UTR_variant	1/3	2		ENSP00000387101.1
HSPD1	ENST00000426480.2	c.-2-1469G>C		intron_variant		4		ENSP00000414446.2
HSPD1	ENST00000345042.6	c.-162G>C		upstream_gene_variant		5		ENSP00000340019.2
HSPE1	ENST00000473395.1	n.-30C>G		upstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.684 AC: 103719 AN: 151714 Hom.: 35849 Cov.: 33

Gnomad AFR AF: 0.756

Gnomad AMI AF: 0.713

Gnomad AMR AF: 0.645

Gnomad ASJ AF: 0.748

Gnomad EAS AF: 0.503

Gnomad SAS AF: 0.694

Gnomad FIN AF: 0.571

Gnomad MID AF: 0.863

Gnomad NFE AF: 0.674

Gnomad OTH AF: 0.707

GnomAD4 exome AF: 0.672 AC: 904201 AN: 1346006 Hom.: 305074 Cov.: 21 AF XY: 0.673 AC XY: 448628 AN XY: 666250

Gnomad4 AFR exome AF: 0.762

Gnomad4 AMR exome AF: 0.534

Gnomad4 ASJ exome AF: 0.748

Gnomad4 EAS exome AF: 0.559

Gnomad4 SAS exome AF: 0.708

Gnomad4 FIN exome AF: 0.580

Gnomad4 NFE exome AF: 0.676

Gnomad4 OTH exome AF: 0.678

GnomAD4 genome AF: 0.684 AC: 103803 AN: 151834 Hom.: 35878 Cov.: 33 AF XY: 0.680 AC XY: 50476 AN XY: 74226

Gnomad4 AFR AF: 0.755

Gnomad4 AMR AF: 0.644

Gnomad4 ASJ AF: 0.748

Gnomad4 EAS AF: 0.504

Gnomad4 SAS AF: 0.694

Gnomad4 FIN AF: 0.571

Gnomad4 NFE AF: 0.674

Gnomad4 OTH AF: 0.707

Alfa AF: 0.530 Hom.: 1371

Bravo AF: 0.689

Asia WGS AF: 0.610 AC: 2124 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 29, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	7.2
DANN	Benign	0.50

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: rs1116734; hg19: chr2-198365043; COSMIC: COSV52098402; COSMIC: COSV52098402;