2-176092982-TGGC-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP3BP6

The NM_000523.4(HOXD13):​c.106_108del​(p.Ala36del) variant causes a inframe deletion change. The variant allele was found at a frequency of 0.0000835 in 1,198,228 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000083 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

HOXD13
NM_000523.4 inframe_deletion

Scores

Not classified

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 3.60
Variant links:
Genes affected
HOXD13 (HGNC:5136): (homeobox D13) 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 in a cluster on chromosome 2. Deletions that remove the entire HOXD gene cluster or the 5' end of this cluster have been associated with severe limb and genital abnormalities. Mutations in this particular gene cause synpolydactyly. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP3
Nonframeshift variant in repetitive region in NM_000523.4
BP6
Variant 2-176092982-TGGC-T is Benign according to our data. Variant chr2-176092982-TGGC-T is described in ClinVar as [Likely_benign]. Clinvar id is 3056120.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr2-176092982-TGGC-T is described in Lovd as [Likely_benign].

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
HOXD13NM_000523.4 linkuse as main transcriptc.106_108del p.Ala36del inframe_deletion 1/2 ENST00000392539.4 NP_000514.2
HOXD13XM_011511068.3 linkuse as main transcriptc.725-1484_725-1482del intron_variant XP_011509370.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
HOXD13ENST00000392539.4 linkuse as main transcriptc.106_108del p.Ala36del inframe_deletion 1/21 NM_000523.4 ENSP00000376322 P1

Frequencies

GnomAD3 genomes
AF:
0.00
AC:
0
AN:
150896
Hom.:
0
Cov.:
33
FAILED QC
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000461
AC:
20
AN:
43376
Hom.:
0
AF XY:
0.000412
AC XY:
11
AN XY:
26720
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000712
Gnomad ASJ exome
AF:
0.000733
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000476
Gnomad FIN exome
AF:
0.000290
Gnomad NFE exome
AF:
0.000394
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000835
AC:
100
AN:
1198228
Hom.:
0
AF XY:
0.000101
AC XY:
59
AN XY:
586168
show subpopulations
Gnomad4 AFR exome
AF:
0.0000421
Gnomad4 AMR exome
AF:
0.000476
Gnomad4 ASJ exome
AF:
0.000323
Gnomad4 EAS exome
AF:
0.0000777
Gnomad4 SAS exome
AF:
0.000583
Gnomad4 FIN exome
AF:
0.000289
Gnomad4 NFE exome
AF:
0.0000446
Gnomad4 OTH exome
AF:
0.0000622
GnomAD4 genome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
150896
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
73650
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

HOXD13-related disorder Benign:1
Likely benign, no assertion criteria providedclinical testingPreventionGenetics, part of Exact SciencesMay 31, 2022This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

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: rs767527649; hg19: chr2-176957710; API