GeneBe

rs201950743

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_007031.2(HSF2BP):​c.856C>G​(p.Pro286Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P286T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 0)

Consequence

HSF2BP
NM_007031.2 missense

Scores

7
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.20

Publications

0 publications found
Variant links:
Genes affected
HSF2BP (HGNC:5226): (heat shock transcription factor 2 binding protein) HSF2 binding protein (HSF2BP) associates with HSF2. The interaction occurs between the trimerization domain of HSF2 and the amino terminal hydrophilic region of HSF2BP that comprises two leucine zipper motifs. HSF2BP may therefore be involved in modulating HSF2 activation. [provided by RefSeq, Jul 2008]
HSF2BP Gene-Disease associations (from GenCC):
  • premature ovarian failure 19
    Inheritance: AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.15952048).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007031.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
HSF2BP
NM_007031.2
MANE Select
c.856C>Gp.Pro286Ala
missense
Exon 9 of 9NP_008962.1Q6IAT7

Ensembl Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
HSF2BP
ENST00000291560.7
TSL:1 MANE Select
c.856C>Gp.Pro286Ala
missense
Exon 9 of 9ENSP00000291560.2O75031-1
HSF2BP
ENST00000913674.1
c.643C>Gp.Pro215Ala
missense
Exon 7 of 7ENSP00000583733.1
HSF2BP
ENST00000869315.1
c.634C>Gp.Pro212Ala
missense
Exon 7 of 7ENSP00000539374.1

Frequencies

GnomAD3 genomes
Cov.:
0
GnomAD2 exomes
AF:
0.0000716
AC:
18
AN:
251298
AF XY:
0.0000663
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000202
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000880
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
Cov.:
0
GnomAD4 genome
Cov.:
0
Alfa
AF:
0.0000936
Hom.:
0
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000576
AC:
7
EpiCase
AF:
0.000109
EpiControl
AF:
0.0000593

ClinVar

ClinVar submissions as Germline
Significance:Uncertain significance
Revision:criteria provided, single submitter
View on ClinVar
Pathogenic
VUS
Benign
Condition
-
1
-
not specified (1)

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.12
BayesDel_addAF
Benign
-0.22
T
BayesDel_noAF
Benign
-0.27
CADD
Benign
21
DANN
Benign
0.97
DEOGEN2
Benign
0.23
T
Eigen
Uncertain
0.40
Eigen_PC
Uncertain
0.43
FATHMM_MKL
Uncertain
0.84
D
LIST_S2
Benign
0.79
T
M_CAP
Benign
0.0054
T
MetaRNN
Benign
0.16
T
MetaSVM
Benign
-0.76
T
PhyloP100
3.2
PrimateAI
Uncertain
0.52
T
PROVEAN
Uncertain
-4.0
D
REVEL
Benign
0.086
Sift
Uncertain
0.020
D
Sift4G
Uncertain
0.056
T
Polyphen
0.86
P
Vest4
0.31
MVP
0.20
MPC
0.077
ClinPred
0.72
D
GERP RS
4.6
Varity_R
0.17
gMVP
0.18
Mutation Taster
=83/17
polymorphism

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

Other links and lift over

dbSNP: rs201950743; hg19: chr21-44949783; API