chr14-64541274-G-A
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Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_021979.4(HSPA2):c.425G>A(p.Ser142Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000558 in 1,613,322 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000033 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000027 ( 0 hom. )
Consequence
HSPA2
NM_021979.4 missense
NM_021979.4 missense
Scores
1
18
Clinical Significance
Conservation
PhyloP100: 3.86
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 Benign. Variant got -8 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.039251387).
BS2
High AC in GnomAd4 at 5 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
HSPA2 | NM_021979.4 | c.425G>A | p.Ser142Asn | missense_variant | 1/1 | ENST00000247207.7 | NP_068814.2 | |
HSPA2 | NM_001387931.1 | c.425G>A | p.Ser142Asn | missense_variant | 2/2 | NP_001374860.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
HSPA2 | ENST00000247207.7 | c.425G>A | p.Ser142Asn | missense_variant | 1/1 | NM_021979.4 | ENSP00000247207 | P1 | ||
HSPA2 | ENST00000394709.2 | c.425G>A | p.Ser142Asn | missense_variant | 2/2 | 1 | ENSP00000378199 | P1 | ||
HSPA2 | ENST00000554883.1 | n.219-63G>A | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 151786Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251188Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135858
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GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461536Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2AN XY: 727086
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GnomAD4 genome AF: 0.0000329 AC: 5AN: 151786Hom.: 0 Cov.: 33 AF XY: 0.0000405 AC XY: 3AN XY: 74088
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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 submitter | clinical testing | Ambry Genetics | Aug 02, 2021 | The c.425G>A (p.S142N) alteration is located in exon 1 (coding exon 1) of the HSPA2 gene. This alteration results from a G to A substitution at nucleotide position 425, causing the serine (S) at amino acid position 142 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
LIST_S2
Benign
.;T
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;N
MutationTaster
Benign
N;N
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
B;B
Vest4
MutPred
Gain of catalytic residue at S142 (P = 0);Gain of catalytic residue at S142 (P = 0);
MVP
ClinPred
T
GERP RS
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gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at