Genetic Variant NM_002145.4:c.365C>A (chr17-48544547-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.74

Variant links:

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 links:

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

HOXB-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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 link	c.365C>A	p.Pro122Gln	missense_variant	Exon 1 of 2	ENST00000330070.6	NP_002136.1	P14652
HOXB2	XM_005257275.5 link	c.-590C>A		5_prime_UTR_variant	Exon 1 of 2		XP_005257332.1
HOXB-AS1	NR_102279.1 link	n.62+135G>T		intron_variant	Intron 1 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
HOXB2	ENST00000330070.6 link	c.365C>A	p.Pro122Gln	missense_variant	Exon 1 of 2	1	NM_002145.4	ENSP00000331741.4	P14652
HOXB-AS1	ENST00000435312.5 link	n.62+135G>T		intron_variant	Intron 1 of 6	5
HOXB-AS1	ENST00000504972.3 link	n.87+910G>T		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000422

AC:

AN:

237068

Hom.:

AF XY:

0.00000772

AC XY:

AN XY:

129574

show subpopulations

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:

AN:

1454004

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

723460

show subpopulations

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.:

ExAC

AF:

0.0000165

AC:

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

BayesDel_noAF

Benign

-0.21

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.11

Eigen

Benign

-0.48

Eigen_PC

Benign

-0.38

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.25

M_CAP

Benign

0.042

MetaRNN

Benign

0.15

MetaSVM

Benign

-0.61

MutationAssessor

Benign

1.2

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-1.1

REVEL

Benign

0.13

Sift

Benign

0.18

Sift4G

Benign

0.34

Polyphen

0.019

Vest4

0.21

MutPred

0.14

Loss of helix (P = 0.0376);

MVP

0.81

MPC

0.43

ClinPred

0.44

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over