17-48543322-A-C

Variant names:

• chr17-48543322-A-C
• rs1195807769
• NM_002145.4:c.817T>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002145.4(HOXB2):​c.817T>G​(p.Ser273Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: HOXB2 NM_002145.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.530
• Publications: 0 publications found

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]

HOXB-AS1 (HGNC:43744): (HOXB cluster antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08924335).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002145.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HOXB2	NM_002145.4	MANE Select	c.817T>G	p.Ser273Ala	missense	Exon 2 of 2	NP_002136.1	P14652

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HOXB2	ENST00000330070.6	TSL:1 MANE Select	c.817T>G	p.Ser273Ala	missense	Exon 2 of 2	ENSP00000331741.4	P14652
	HOXB-AS1	ENST00000504972.4	TSL:3	n.9A>C		non_coding_transcript_exon	Exon 1 of 2
	HOXB2	ENST00000571287.1	TSL:3	n.462T>G		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.054
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	1.2
DANN	Benign	0.25
DEOGEN2	Benign	0.078	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.14	T
M_CAP	Pathogenic	0.46	D
MetaRNN	Benign	0.089	T
MetaSVM	Benign	-0.74	T
MutationAssessor	Benign	0.69	N
PhyloP100		-0.53
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-0.61	N
REVEL	Benign	0.16
Sift	Benign	0.64	T
Sift4G	Benign	0.65	T
Polyphen		0.0	B
Vest4		0.066
MutPred		0.25		Loss of phosphorylation at S273 (P = 0.0306)
MVP		0.45
MPC		0.26
ClinPred		0.052	T
GERP RS		-2.4
Varity_R		0.042
gMVP		0.12

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

Other links and lift over

dbSNP: rs1195807769; hg19: chr17-46620684;