17-48544547-G-T

Variant names:

• chr17-48544547-G-T
• rs777610889
• NM_002145.4:c.365C>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.365C>A​(p.Pro122Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,454,004 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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: 2.74

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=0.14741063).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HOXB2	NM_002145.4	c.365C>A	p.Pro122Gln	missense_variant	Exon 1 of 2	ENST00000330070.6	NP_002136.1
HOXB2	XM_005257275.5	c.-590C>A		5_prime_UTR_variant	Exon 1 of 2		XP_005257332.1
HOXB-AS1	NR_102279.1	n.62+135G>T		intron_variant	Intron 1 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HOXB2	ENST00000330070.6	c.365C>A	p.Pro122Gln	missense_variant	Exon 1 of 2	1	NM_002145.4	ENSP00000331741.4
HOXB-AS1	ENST00000435312.5	n.62+135G>T		intron_variant	Intron 1 of 6	5
HOXB-AS1	ENST00000504972.3	n.87+910G>T		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.00000422 AC: 1 AN: 237068 Hom.: 0 AF XY: 0.00000772 AC XY: 1 AN XY: 129574

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: 0.0000330

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1454004 Hom.: 0 Cov.: 38 AF XY: 0.00000138 AC XY: 1 AN XY: 723460

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: 0.0000165 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Uncertain	0.020	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	18
DANN	Benign	0.95
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.38
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.25	T
M_CAP	Benign	0.042	D
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.61	T
MutationAssessor	Benign	1.2	L
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.13
Sift	Benign	0.18	T
Sift4G	Benign	0.34	T
Polyphen		0.019	B
Vest4		0.21
MutPred		0.14		Loss of helix (P = 0.0376);
MVP		0.81
MPC		0.43
ClinPred		0.44	T
GERP RS		1.5
Varity_R		0.040
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

Publications

LitVar

Other links and lift over

dbSNP: rs777610889; hg19: chr17-46621909;