chr17-48544577-G-T

Variant names:

• chr17-48544577-G-T
• rs142902653
• NM_002145.4:c.335C>A

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.335C>A​(p.Thr112Lys) 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. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T112M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: HOXB2 NM_002145.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.25
• Publications: 1 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=0.1567541).

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.335C>A	p.Thr112Lys	missense	Exon 1 of 2	NP_002136.1	P14652
	HOXB-AS1	NR_102279.1		n.62+165G>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HOXB2	ENST00000330070.6	TSL:1 MANE Select	c.335C>A	p.Thr112Lys	missense	Exon 1 of 2	ENSP00000331741.4	P14652
	HOXB-AS1	ENST00000717407.1		n.416G>T		non_coding_transcript_exon	Exon 2 of 3
	HOXB-AS1	ENST00000717408.1		n.349G>T		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00 AC: 0 AN: 239928 AF XY: 0.00

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1455980 Hom.: 0 Cov.: 38 AF XY: 0.00 AC XY: 0 AN XY: 724444

African (AFR) AF: 0.00 AC: 0 AN: 33434

American (AMR) AF: 0.00 AC: 0 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26014

East Asian (EAS) AF: 0.00 AC: 0 AN: 39676

South Asian (SAS) AF: 0.00 AC: 0 AN: 86108

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48770

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5096

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111924

Other (OTH) AF: 0.00 AC: 0 AN: 60246

GnomAD4 genome Cov.: 31

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Uncertain	0.016	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	21
DANN	Benign	0.95
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.16
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.37	T
M_CAP	Benign	0.056	D
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.59	T
MutationAssessor	Benign	1.4	L
PhyloP100		2.3
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.19
Sift	Benign	0.14	T
Sift4G	Benign	0.48	T
Polyphen		0.12	B
Vest4		0.18
MutPred		0.37		Loss of phosphorylation at T112 (P = 0.0093)
MVP		0.85
MPC		0.45
ClinPred		0.53	D
GERP RS		3.8
Varity_R		0.23
gMVP		0.27

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: rs142902653; hg19: chr17-46621939;