chr21-43529816-G-A

Variant names:

• chr21-43529816-G-A
• rs368184709
• NM_007031.2:c.943C>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_007031.2(HSF2BP):​c.943C>T​(p.Arg315Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 0)
• Consequence: HSF2BP NM_007031.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.08

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.19450471).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSF2BP	NM_007031.2	c.943C>T	p.Arg315Cys	missense_variant	Exon 9 of 9	ENST00000291560.7	NP_008962.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HSF2BP	ENST00000291560.7	c.943C>T	p.Arg315Cys	missense_variant	Exon 9 of 9	1	NM_007031.2	ENSP00000291560.2

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD3 exomes AF: 0.0000119 AC: 3 AN: 251180 Hom.: 0 AF XY: 0.00000737 AC XY: 1 AN XY: 135746

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 0

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 18, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.943C>T (p.R315C) alteration is located in exon 9 (coding exon 8) of the HSF2BP gene. This alteration results from a C to T substitution at nucleotide position 943, causing the arginine (R) at amino acid position 315 to be replaced by a cysteine (C). 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	0.075
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.054	T
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.29
FATHMM_MKL	Benign	0.072	N
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.0	N
PrimateAI	Benign	0.20	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.10
Sift	Uncertain	0.018	D
Sift4G	Uncertain	0.042	D
Polyphen		0.61	P
Vest4		0.11
MVP		0.63
MPC		0.11
ClinPred		0.44	T
GERP RS		3.6
Varity_R		0.11
gMVP		0.070

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

Other links and lift over

dbSNP: rs368184709; hg19: chr21-44949696;