chr14-64540868-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_021979.4(HSPA2):​c.19G>T​(p.Ala7Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000496 in 1,613,994 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

HSPA2
NM_021979.4 missense

Scores

1
4
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.57
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.19994348).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
HSPA2NM_021979.4 linkuse as main transcriptc.19G>T p.Ala7Ser missense_variant 1/1 ENST00000247207.7 NP_068814.2
HSPA2NM_001387931.1 linkuse as main transcriptc.19G>T p.Ala7Ser missense_variant 2/2 NP_001374860.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
HSPA2ENST00000247207.7 linkuse as main transcriptc.19G>T p.Ala7Ser missense_variant 1/1 NM_021979.4 ENSP00000247207 P1
HSPA2ENST00000394709.2 linkuse as main transcriptc.19G>T p.Ala7Ser missense_variant 2/21 ENSP00000378199 P1
HSPA2ENST00000554883.1 linkuse as main transcriptn.128G>T non_coding_transcript_exon_variant 1/23

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152196
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000724
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000119
AC:
3
AN:
251154
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135746
show subpopulations
Gnomad AFR exome
AF:
0.000123
Gnomad AMR exome
AF:
0.0000289
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000274
AC:
4
AN:
1461798
Hom.:
0
Cov.:
29
AF XY:
0.00000138
AC XY:
1
AN XY:
727196
show subpopulations
Gnomad4 AFR exome
AF:
0.0000896
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152196
Hom.:
0
Cov.:
33
AF XY:
0.0000269
AC XY:
2
AN XY:
74342
show subpopulations
Gnomad4 AFR
AF:
0.0000724
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000453
ExAC
AF:
0.00000824
AC:
1
Asia WGS
AF:
0.000866
AC:
3
AN:
3478

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsMay 30, 2024The c.19G>T (p.A7S) alteration is located in exon 1 (coding exon 1) of the HSPA2 gene. This alteration results from a G to T substitution at nucleotide position 19, causing the alanine (A) at amino acid position 7 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.18
BayesDel_addAF
Benign
-0.34
T
BayesDel_noAF
Benign
-0.50
CADD
Uncertain
24
DANN
Uncertain
0.98
DEOGEN2
Benign
0.11
T;T
Eigen
Benign
0.17
Eigen_PC
Uncertain
0.33
FATHMM_MKL
Benign
0.72
D
LIST_S2
Uncertain
0.93
.;D
M_CAP
Benign
0.026
D
MetaRNN
Benign
0.20
T;T
MetaSVM
Benign
-0.79
T
MutationAssessor
Uncertain
2.6
M;M
MutationTaster
Benign
0.99
D;D
PrimateAI
Pathogenic
0.81
D
PROVEAN
Benign
-1.4
N;N
REVEL
Benign
0.18
Sift
Benign
0.079
T;T
Sift4G
Benign
0.088
T;T
Polyphen
0.0040
B;B
Vest4
0.16
MutPred
0.62
Gain of catalytic residue at G5 (P = 0.0012);Gain of catalytic residue at G5 (P = 0.0012);
MVP
0.53
ClinPred
0.68
D
GERP RS
5.4
Varity_R
0.45
gMVP
0.74

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.

Other links and lift over

dbSNP: rs751675059; hg19: chr14-65007586; API