21-43613890-A-C

Position:

• chr21-43613890-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_007031.2(HSF2BP):​c.632T>G​(p.Leu211Trp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: HSF2BP NM_007031.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.28

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HSF2BP	NM_007031.2	c.632T>G	p.Leu211Trp	missense_variant	7/9	ENST00000291560.7	NP_008962.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HSF2BP	ENST00000291560.7	c.632T>G	p.Leu211Trp	missense_variant	7/9	1	NM_007031.2	ENSP00000291560.2
HSF2BP	ENST00000443485.1	c.641T>G	p.Leu214Trp	missense_variant	7/7	5		ENSP00000409585.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 20, 2024

The c.632T>G (p.L211W) alteration is located in exon 7 (coding exon 6) of the HSF2BP gene. This alteration results from a T to G substitution at nucleotide position 632, causing the leucine (L) at amino acid position 211 to be replaced by a tryptophan (W). 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	Pathogenic	0.78
BayesDel_addAF	Pathogenic	0.31	D
BayesDel_noAF	Pathogenic	0.20
CADD	Pathogenic	27
DANN	Benign	0.96
DEOGEN2	Benign	0.29	T;T
Eigen	Pathogenic	0.74
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.83	T;T
M_CAP	Benign	0.057	D
MetaRNN	Uncertain	0.72	D;D
MetaSVM	Uncertain	-0.070	T
MutationAssessor	Uncertain	2.3	M;.
PrimateAI	Uncertain	0.71	T
PROVEAN	Uncertain	-3.4	D;D
REVEL	Uncertain	0.46
Sift	Uncertain	0.0020	D;D
Sift4G	Uncertain	0.0020	D;.
Polyphen		1.0	D;.
Vest4		0.93
MutPred		0.38		Loss of stability (P = 0.0291);.;
MVP		0.64
MPC		0.48
ClinPred		0.98	D
GERP RS		5.8
Varity_R		0.61
gMVP		0.79

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: chr21-45033771;