rs2229302

Positions:

• chr17-48543040-G-A
• chr17-48543040-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002145.4(HOXB2):​c.*28C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.18 in 1,532,648 control chromosomes in the GnomAD database, including 26,203 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.16 (2080 hom., cov: 31)
  • Exomes 𝑓: 0.18 (24123 hom.)
• Consequence: HOXB2 NM_002145.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.289

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]

HOXB2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.193 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HOXB2	NM_002145.4	c.*28C>T		3_prime_UTR_variant	2/2	ENST00000330070.6	NP_002136.1
HOXB2	XM_005257275.5	c.*28C>T		3_prime_UTR_variant	2/2		XP_005257332.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HOXB2	ENST00000330070.6	c.*28C>T		3_prime_UTR_variant	2/2	1	NM_002145.4	ENSP00000331741.4
HOXB2	ENST00000504772.3	n.107C>T		non_coding_transcript_exon_variant	1/2	3

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23747 AN: 152002 Hom.: 2078 Cov.: 31

Gnomad AFR AF: 0.0810

Gnomad AMI AF: 0.296

Gnomad AMR AF: 0.156

Gnomad ASJ AF: 0.183

Gnomad EAS AF: 0.0871

Gnomad SAS AF: 0.129

Gnomad FIN AF: 0.222

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.195

Gnomad OTH AF: 0.167

GnomAD3 exomes AF: 0.163 AC: 31811 AN: 195640 Hom.: 2921 AF XY: 0.165 AC XY: 17433 AN XY: 105586

Gnomad AFR exome AF: 0.0771

Gnomad AMR exome AF: 0.134

Gnomad ASJ exome AF: 0.185

Gnomad EAS exome AF: 0.0802

Gnomad SAS exome AF: 0.114

Gnomad FIN exome AF: 0.222

Gnomad NFE exome AF: 0.192

Gnomad OTH exome AF: 0.174

GnomAD4 exome AF: 0.182 AC: 251816 AN: 1380528 Hom.: 24123 Cov.: 29 AF XY: 0.181 AC XY: 123044 AN XY: 680812

Gnomad4 AFR exome AF: 0.0758

Gnomad4 AMR exome AF: 0.138

Gnomad4 ASJ exome AF: 0.192

Gnomad4 EAS exome AF: 0.0546

Gnomad4 SAS exome AF: 0.120

Gnomad4 FIN exome AF: 0.221

Gnomad4 NFE exome AF: 0.194

Gnomad4 OTH exome AF: 0.174

GnomAD4 genome AF: 0.156 AC: 23754 AN: 152120 Hom.: 2080 Cov.: 31 AF XY: 0.157 AC XY: 11661 AN XY: 74370

Gnomad4 AFR AF: 0.0811

Gnomad4 AMR AF: 0.156

Gnomad4 ASJ AF: 0.183

Gnomad4 EAS AF: 0.0868

Gnomad4 SAS AF: 0.130

Gnomad4 FIN AF: 0.222

Gnomad4 NFE AF: 0.195

Gnomad4 OTH AF: 0.165

Alfa AF: 0.169 Hom.: 2046

Bravo AF: 0.148

Asia WGS AF: 0.132 AC: 460 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.3
DANN	Benign	0.74
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs2229302; hg19: chr17-46620402;