chr14-64541742-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_021979.4(HSPA2):​c.893C>T​(p.Thr298Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000118 in 1,611,978 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

HSPA2
NM_021979.4 missense

Scores

4
9
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.91
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 -4 ACMG points.

BS2
High AC in GnomAdExome4 at 18 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
HSPA2NM_021979.4 linkuse as main transcriptc.893C>T p.Thr298Met missense_variant 1/1 ENST00000247207.7 NP_068814.2
HSPA2NM_001387931.1 linkuse as main transcriptc.893C>T p.Thr298Met 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.893C>T p.Thr298Met missense_variant 1/1 NM_021979.4 ENSP00000247207 P1
HSPA2ENST00000394709.2 linkuse as main transcriptc.893C>T p.Thr298Met missense_variant 2/21 ENSP00000378199 P1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152228
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.0000245
AC:
6
AN:
245020
Hom.:
0
AF XY:
0.0000375
AC XY:
5
AN XY:
133308
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.000504
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000912
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000123
AC:
18
AN:
1459750
Hom.:
0
Cov.:
86
AF XY:
0.0000138
AC XY:
10
AN XY:
726166
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.000345
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000720
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152228
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
74370
show subpopulations
Gnomad4 AFR
AF:
0.00
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
Alfa
AF:
0.0000868
Hom.:
0
Bravo
AF:
0.00000756
ExAC
AF:
0.0000165
AC:
2

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 GeneticsOct 12, 2023The c.893C>T (p.T298M) alteration is located in exon 1 (coding exon 1) of the HSPA2 gene. This alteration results from a C to T substitution at nucleotide position 893, causing the threonine (T) at amino acid position 298 to be replaced by a methionine (M). 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
0.31
BayesDel_addAF
Uncertain
0.16
D
BayesDel_noAF
Uncertain
-0.010
CADD
Pathogenic
31
DANN
Uncertain
1.0
DEOGEN2
Benign
0.21
T;T
Eigen
Pathogenic
0.70
Eigen_PC
Pathogenic
0.68
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Uncertain
0.97
.;D
M_CAP
Benign
0.039
D
MetaRNN
Uncertain
0.67
D;D
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.0
L;L
MutationTaster
Benign
1.0
D;D
PrimateAI
Pathogenic
0.81
D
PROVEAN
Uncertain
-3.8
D;D
REVEL
Uncertain
0.42
Sift
Pathogenic
0.0
D;D
Sift4G
Uncertain
0.0090
D;D
Polyphen
1.0
D;D
Vest4
0.64
MutPred
0.65
Gain of catalytic residue at V294 (P = 0);Gain of catalytic residue at V294 (P = 0);
MVP
0.41
ClinPred
0.95
D
GERP RS
4.9
Varity_R
0.93
gMVP
0.80

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: rs370673877; hg19: chr14-65008460; API