chr14-64541183-A-T
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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.334A>T(p.Thr112Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000527 in 1,614,112 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000057 ( 3 hom. )
Consequence
HSPA2
NM_021979.4 missense
NM_021979.4 missense
Scores
19
Clinical Significance
Conservation
PhyloP100: 1.90
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=0.036224335).
BS2
High AC in GnomAdExome4 at 83 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
HSPA2 | NM_021979.4 | c.334A>T | p.Thr112Ser | missense_variant | 1/1 | ENST00000247207.7 | NP_068814.2 | |
HSPA2 | NM_001387931.1 | c.334A>T | p.Thr112Ser | missense_variant | 2/2 | NP_001374860.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
HSPA2 | ENST00000247207.7 | c.334A>T | p.Thr112Ser | missense_variant | 1/1 | NM_021979.4 | ENSP00000247207 | P1 | ||
HSPA2 | ENST00000394709.2 | c.334A>T | p.Thr112Ser | missense_variant | 2/2 | 1 | ENSP00000378199 | P1 | ||
HSPA2 | ENST00000554883.1 | n.219-154A>T | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152144Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000995 AC: 25AN: 251316Hom.: 2 AF XY: 0.000169 AC XY: 23AN XY: 135854
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GnomAD4 exome AF: 0.0000568 AC: 83AN: 1461850Hom.: 3 Cov.: 30 AF XY: 0.0000880 AC XY: 64AN XY: 727228
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GnomAD4 genome AF: 0.0000131 AC: 2AN: 152262Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74446
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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 | Feb 14, 2023 | The c.334A>T (p.T112S) alteration is located in exon 1 (coding exon 1) of the HSPA2 gene. This alteration results from a A to T substitution at nucleotide position 334, causing the threonine (T) at amino acid position 112 to be replaced by a serine (S). 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
L;L
MutationTaster
Benign
N;N
PrimateAI
Benign
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 E107 (P = 0.0081);Gain of catalytic residue at E107 (P = 0.0081);
MVP
ClinPred
T
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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