2-176157430-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_006898.5(HOXD3):​c.-203C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.765 in 152,002 control chromosomes in the GnomAD database, including 45,146 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 0.76 ( 45146 hom., cov: 32)

Consequence

HOXD3
NM_006898.5 5_prime_UTR

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.32
Variant links:
Genes affected
HOXD3 (HGNC:5137): (homeobox D3) This gene belongs to the homeobox family of genes. The homeobox genes encode a highly conserved family of transcription factors that play an important role in morphogenesis in all multicellular organisms. Mammals possess four similar homeobox gene clusters, HOXA, HOXB, HOXC and HOXD, located on different chromosomes, consisting of 9 to 11 genes arranged in tandem. This gene is one of several homeobox HOXD genes located at 2q31-2q37 chromosome regions. Deletions that removed the entire HOXD gene cluster or 5' end of this cluster have been associated with severe limb and genital abnormalities. The protein encoded by this gene may play a role in the regulation of cell adhesion processes. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.71).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.887 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
HOXD3NM_006898.5 linkuse as main transcriptc.-203C>G 5_prime_UTR_variant 1/4 ENST00000683222.1 NP_008829.3 P31249

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
HOXD3ENST00000683222.1 linkuse as main transcriptc.-203C>G 5_prime_UTR_variant 1/4 NM_006898.5 ENSP00000507129.1 P31249
HOXD3ENST00000432796.2 linkuse as main transcriptc.-84-11601C>G intron_variant 3 ENSP00000392615.2 C9J1M3

Frequencies

GnomAD3 genomes
AF:
0.765
AC:
116133
AN:
151892
Hom.:
45083
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.894
Gnomad AMI
AF:
0.731
Gnomad AMR
AF:
0.792
Gnomad ASJ
AF:
0.733
Gnomad EAS
AF:
0.743
Gnomad SAS
AF:
0.861
Gnomad FIN
AF:
0.703
Gnomad MID
AF:
0.778
Gnomad NFE
AF:
0.686
Gnomad OTH
AF:
0.766
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.765
AC:
116249
AN:
152002
Hom.:
45146
Cov.:
32
AF XY:
0.768
AC XY:
57049
AN XY:
74310
show subpopulations
Gnomad4 AFR
AF:
0.894
Gnomad4 AMR
AF:
0.792
Gnomad4 ASJ
AF:
0.733
Gnomad4 EAS
AF:
0.743
Gnomad4 SAS
AF:
0.862
Gnomad4 FIN
AF:
0.703
Gnomad4 NFE
AF:
0.686
Gnomad4 OTH
AF:
0.766
Alfa
AF:
0.639
Hom.:
2025
Bravo
AF:
0.776

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.71
CADD
Benign
15
DANN
Benign
0.83

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.

Other links and lift over

dbSNP: rs2551802; hg19: chr2-177022158; API