14-64537173-A-C

Position:

• chr14-64537173-A-C

Variant summary

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

The ENST00000394709.2(HSPA2):​c.-6+1198A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.635 in 151,930 control chromosomes in the GnomAD database, including 31,944 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 0.63 (31944 hom., cov: 31)
• Consequence: HSPA2 ENST00000394709.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.475

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]

HSPA2-AS1 (HGNC:55433): (HSPA2 and ZBTB1 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.835 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HSPA2-AS1	NR_110550.1	n.52+3144T>G		intron_variant, non_coding_transcript_variant
HSPA2	NM_001387931.1	c.-6+1198A>C		intron_variant			NP_001374860.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HSPA2	ENST00000394709.2	c.-6+1198A>C		intron_variant		1		ENSP00000378199	P1
HSPA2-AS1	ENST00000554918.1	n.52+3144T>G		intron_variant, non_coding_transcript_variant		3
HSPA2-AS1	ENST00000648003.1	n.474+1975T>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.635 AC: 96368 AN: 151812 Hom.: 31930 Cov.: 31

Gnomad AFR AF: 0.435

Gnomad AMI AF: 0.737

Gnomad AMR AF: 0.706

Gnomad ASJ AF: 0.656

Gnomad EAS AF: 0.857

Gnomad SAS AF: 0.715

Gnomad FIN AF: 0.835

Gnomad MID AF: 0.596

Gnomad NFE AF: 0.684

Gnomad OTH AF: 0.635

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.635 AC: 96406 AN: 151930 Hom.: 31944 Cov.: 31 AF XY: 0.646 AC XY: 47929 AN XY: 74238

Gnomad4 AFR AF: 0.435

Gnomad4 AMR AF: 0.706

Gnomad4 ASJ AF: 0.656

Gnomad4 EAS AF: 0.856

Gnomad4 SAS AF: 0.714

Gnomad4 FIN AF: 0.835

Gnomad4 NFE AF: 0.684

Gnomad4 OTH AF: 0.636

Alfa AF: 0.626 Hom.: 4393

Bravo AF: 0.615

Asia WGS AF: 0.719 AC: 2502 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	8.2
DANN	Benign	0.84

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs7151976; hg19: chr14-65003891;