17-48544731-A-G
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Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BS2
The NM_002145.4(HOXB2):āc.181T>Cā(p.Ser61Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,736 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: not found (cov: 31)
Exomes š: 0.0000034 ( 0 hom. )
Consequence
HOXB2
NM_002145.4 missense
NM_002145.4 missense
Scores
9
10
Clinical Significance
Conservation
PhyloP100: 2.19
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 -2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BS2
High AC in GnomAdExome4 at 5 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HOXB2 | NM_002145.4 | c.181T>C | p.Ser61Pro | missense_variant | 1/2 | ENST00000330070.6 | |
HOXB-AS1 | NR_102279.1 | n.62+319A>G | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HOXB2 | ENST00000330070.6 | c.181T>C | p.Ser61Pro | missense_variant | 1/2 | 1 | NM_002145.4 | P1 | |
HOXB-AS1 | ENST00000435312.5 | n.62+319A>G | intron_variant, non_coding_transcript_variant | 5 | |||||
HOXB-AS1 | ENST00000504972.3 | n.88-764A>G | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD3 genomes
Cov.:
31
GnomAD3 exomes AF: 0.0000200 AC: 5AN: 249874Hom.: 0 AF XY: 0.0000295 AC XY: 4AN XY: 135526
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GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461736Hom.: 0 Cov.: 37 AF XY: 0.00000550 AC XY: 4AN XY: 727158
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GnomAD4 genome Cov.: 31
GnomAD4 genome
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31
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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 | Apr 26, 2023 | The c.181T>C (p.S61P) alteration is located in exon 1 (coding exon 1) of the HOXB2 gene. This alteration results from a T to C substitution at nucleotide position 181, causing the serine (S) at amino acid position 61 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
Uncertain
D
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
M_CAP
Uncertain
D
MetaRNN
Uncertain
T
MetaSVM
Uncertain
T
MutationAssessor
Benign
N
MutationTaster
Benign
N
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Uncertain
Sift
Benign
T
Sift4G
Benign
T
Polyphen
P
Vest4
MutPred
Loss of phosphorylation at S61 (P = 0.0398);
MVP
MPC
ClinPred
D
GERP RS
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