Variant 14-64542508-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_021979.4(HSPA2):c.1659G>A(p.Lys553=) variant causes a synonymous change. The variant allele was found at a frequency of 0.00355 in 1,613,384 control chromosomes in the GnomAD database, including 173 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.019 ( 81 hom., cov: 31)

Exomes 𝑓: 0.0020 ( 92 hom. )

Consequence

HSPA2
NM_021979.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.66

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BP6

Variant 14-64542508-G-A is Benign according to our data. Variant chr14-64542508-G-A is described in ClinVar as [Benign]. Clinvar id is 779688.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0633 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HSPA2	NM_021979.4 linkuse as main transcript	c.1659G>A	p.Lys553=	synonymous_variant	1/1	ENST00000247207.7	NP_068814.2
HSPA2	NM_001387931.1 linkuse as main transcript	c.1659G>A	p.Lys553=	synonymous_variant	2/2		NP_001374860.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HSPA2	ENST00000247207.7 linkuse as main transcript	c.1659G>A	p.Lys553=	synonymous_variant	1/1		NM_021979.4	ENSP00000247207	P1
HSPA2	ENST00000394709.2 linkuse as main transcript	c.1659G>A	p.Lys553=	synonymous_variant	2/2	1		ENSP00000378199	P1

Frequencies

GnomAD3 genomes

AF:

0.0187

AC:

2828

AN:

151580

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0655

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00586

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.0130

GnomAD3 exomes

AF:

0.00519

AC:

1302

AN:

250704

Hom.:

AF XY:

0.00371

AC XY:

504

AN XY:

135678

show subpopulations

Gnomad AFR exome

AF:

0.0704

Gnomad AMR exome

AF:

0.00353

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000221

Gnomad OTH exome

AF:

0.00245

GnomAD4 exome

AF:

0.00198

AC:

2890

AN:

1461686

Hom.:

Cov.:

AF XY:

0.00169

AC XY:

1226

AN XY:

727122

show subpopulations

Gnomad4 AFR exome

AF:

0.0689

Gnomad4 AMR exome

AF:

0.00356

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000696

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000998

Gnomad4 OTH exome

AF:

0.00477

GnomAD4 genome

AF:

0.0187

AC:

2831

AN:

151698

Hom.:

Cov.:

AF XY:

0.0184

AC XY:

1362

AN XY:

74080

show subpopulations

Gnomad4 AFR

AF:

0.0653

Gnomad4 AMR

AF:

0.00585

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000191

Gnomad4 OTH

AF:

0.0128

Alfa

AF:

0.00909

Hom.:

Bravo

AF:

0.0222

Asia WGS

AF:

0.00491

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.000474

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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	Labcorp Genetics (formerly Invitae), Labcorp	Jun 05, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Benign

0.94

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over