chr17-48543457-G-T

Variant names:

• chr17-48543457-G-T
• rs779320754
• NM_002145.4:c.682C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002145.4(HOXB2):​c.682C>A​(p.Pro228Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,454,762 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: HOXB2 NM_002145.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.758

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18433705).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HOXB2	NM_002145.4	c.682C>A	p.Pro228Thr	missense_variant	Exon 2 of 2	ENST00000330070.6	NP_002136.1
HOXB2	XM_005257275.5	c.355C>A	p.Pro119Thr	missense_variant	Exon 2 of 2		XP_005257332.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HOXB2	ENST00000330070.6	c.682C>A	p.Pro228Thr	missense_variant	Exon 2 of 2	1	NM_002145.4	ENSP00000331741.4
HOXB2	ENST00000571287.1	n.327C>A		non_coding_transcript_exon_variant	Exon 2 of 2	3
HOXB-AS1	ENST00000504972.3	n.-94G>T		upstream_gene_variant		3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.00000428 AC: 1 AN: 233502 Hom.: 0 AF XY: 0.00000775 AC XY: 1 AN XY: 129014

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000333

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1454762 Hom.: 0 Cov.: 33 AF XY: 0.00000276 AC XY: 2 AN XY: 723450

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000233

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ExAC AF: 0.00000846 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	2.7
DANN	Benign	0.69
DEOGEN2	Benign	0.23	T
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.78
FATHMM_MKL	Benign	0.50	N
LIST_S2	Benign	0.43	T
M_CAP	Pathogenic	0.49	D
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.48	T
MutationAssessor	Uncertain	2.1	M
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.21
Sift	Benign	0.21	T
Sift4G	Benign	0.26	T
Polyphen		0.73	P
Vest4		0.091
MutPred		0.17		Gain of phosphorylation at P228 (P = 0.0668);
MVP		0.88
MPC		0.40
ClinPred		0.13	T
GERP RS		3.0
Varity_R		0.062
gMVP		0.22

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: rs779320754; hg19: chr17-46620819;