14-64543642-C-G

Position:

• chr14-64543642-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000394709.2(HSPA2):​c.*873C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.636 in 152,102 control chromosomes in the GnomAD database, including 32,170 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 0.64 (32169 hom., cov: 33)
  • Exomes 𝑓: 1.0 (1 hom.)
• Consequence: HSPA2 ENST00000394709.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.08

Genes affected

HSPA2 (HGNC:5235): (heat shock protein family A (Hsp70) member 2) Enables disordered domain specific binding activity; enzyme binding activity; and unfolded protein binding activity. Involved in negative regulation of inclusion body assembly and protein refolding. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.868 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HSPA2	ENST00000394709.2	c.*873C>G		3_prime_UTR_variant	2/2	1		P1

Frequencies

GnomAD3 genomes AF: 0.636 AC: 96709 AN: 151982 Hom.: 32157 Cov.: 33

Gnomad AFR AF: 0.437

Gnomad AMI AF: 0.737

Gnomad AMR AF: 0.706

Gnomad ASJ AF: 0.656

Gnomad EAS AF: 0.890

Gnomad SAS AF: 0.714

Gnomad FIN AF: 0.835

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.684

Gnomad OTH AF: 0.638

GnomAD4 exome AF: 1.00 AC: 2 AN: 2 Hom.: 1 Cov.: 0 AC XY: 0 AN XY: 0

Gnomad4 FIN exome AF: 1.00

GnomAD4 genome AF: 0.636 AC: 96744 AN: 152100 Hom.: 32169 Cov.: 33 AF XY: 0.647 AC XY: 48137 AN XY: 74354

Gnomad4 AFR AF: 0.436

Gnomad4 AMR AF: 0.706

Gnomad4 ASJ AF: 0.656

Gnomad4 EAS AF: 0.890

Gnomad4 SAS AF: 0.713

Gnomad4 FIN AF: 0.835

Gnomad4 NFE AF: 0.684

Gnomad4 OTH AF: 0.640

Alfa AF: 0.652 Hom.: 4104

Bravo AF: 0.617

Asia WGS AF: 0.728 AC: 2534 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	12
DANN	Benign	0.61

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: rs11848114; hg19: chr14-65010360;