chr14-64542257-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_021979.4(HSPA2):​c.1408G>T​(p.Ala470Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Consequence

HSPA2
NM_021979.4 missense

Scores

2
7
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.79
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.3541644).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
HSPA2NM_021979.4 linkuse as main transcriptc.1408G>T p.Ala470Ser missense_variant 1/1 ENST00000247207.7 NP_068814.2
HSPA2NM_001387931.1 linkuse as main transcriptc.1408G>T p.Ala470Ser 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.1408G>T p.Ala470Ser missense_variant 1/1 NM_021979.4 ENSP00000247207 P1
HSPA2ENST00000394709.2 linkuse as main transcriptc.1408G>T p.Ala470Ser missense_variant 2/21 ENSP00000378199 P1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
Cov.:
86
GnomAD4 genome
Cov.:
31

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 GeneticsFeb 28, 2023The c.1408G>T (p.A470S) 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 1408, causing the alanine (A) at amino acid position 470 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
0.30
BayesDel_addAF
Benign
-0.048
T
BayesDel_noAF
Benign
-0.31
CADD
Pathogenic
26
DANN
Uncertain
0.99
DEOGEN2
Benign
0.14
T;T
Eigen
Uncertain
0.43
Eigen_PC
Uncertain
0.40
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Uncertain
0.94
.;D
M_CAP
Benign
0.021
T
MetaRNN
Benign
0.35
T;T
MetaSVM
Benign
-1.2
T
MutationAssessor
Pathogenic
3.2
M;M
MutationTaster
Benign
1.0
D;D
PrimateAI
Pathogenic
0.80
T
PROVEAN
Benign
-2.3
N;N
REVEL
Benign
0.26
Sift
Uncertain
0.015
D;D
Sift4G
Uncertain
0.011
D;D
Polyphen
0.39
B;B
Vest4
0.32
MutPred
0.65
Gain of catalytic residue at P469 (P = 0);Gain of catalytic residue at P469 (P = 0);
MVP
0.41
ClinPred
0.99
D
GERP RS
5.1
Varity_R
0.33
gMVP
0.57

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-65008975; API