chr17-48543130-A-G
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Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_002145.4(HOXB2):āc.1009T>Cā(p.Ser337Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00121 in 1,611,654 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.00068 ( 0 hom., cov: 31)
Exomes š: 0.0013 ( 1 hom. )
Consequence
HOXB2
NM_002145.4 missense
NM_002145.4 missense
Scores
1
5
13
Clinical Significance
Conservation
PhyloP100: 6.96
Genes affected
HOXB2 (HGNC:5113): (homeobox B2) This gene is a member of the Antp homeobox family and encodes a nuclear protein with a homeobox DNA-binding domain. It is included in a cluster of homeobox B genes located on chromosome 17. The encoded protein functions as a sequence-specific transcription factor that is involved in development. Increased expression of this gene is associated with pancreatic cancer. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.2265436).
BS2
High AC in GnomAd4 at 104 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HOXB2 | NM_002145.4 | c.1009T>C | p.Ser337Pro | missense_variant | 2/2 | ENST00000330070.6 | |
HOXB2 | XM_005257275.5 | c.682T>C | p.Ser228Pro | missense_variant | 2/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HOXB2 | ENST00000330070.6 | c.1009T>C | p.Ser337Pro | missense_variant | 2/2 | 1 | NM_002145.4 | P1 | |
HOXB2 | ENST00000504772.3 | n.17T>C | non_coding_transcript_exon_variant | 1/2 | 3 | ||||
HOXB2 | ENST00000571287.1 | downstream_gene_variant | 3 |
Frequencies
GnomAD3 genomes AF: 0.000684 AC: 104AN: 152024Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.000675 AC: 168AN: 248784Hom.: 0 AF XY: 0.000757 AC XY: 102AN XY: 134658
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GnomAD4 exome AF: 0.00126 AC: 1845AN: 1459630Hom.: 1 Cov.: 33 AF XY: 0.00116 AC XY: 839AN XY: 726202
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GnomAD4 genome AF: 0.000684 AC: 104AN: 152024Hom.: 0 Cov.: 31 AF XY: 0.000687 AC XY: 51AN XY: 74266
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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 | Dec 16, 2023 | The c.1009T>C (p.S337P) alteration is located in exon 2 (coding exon 2) of the HOXB2 gene. This alteration results from a T to C substitution at nucleotide position 1009, causing the serine (S) at amino acid position 337 to be replaced by a proline (P). 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
Uncertain
DEOGEN2
Uncertain
D
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D
REVEL
Benign
Sift
Benign
D
Sift4G
Benign
T
Polyphen
P
Vest4
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
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