chr2-176093057-G-GGGC

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 0P and 3B. BP3BP6_Moderate

The NM_000523.4(HOXD13):​c.180_182dup​(p.Ala70dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000245 in 150,896 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00025 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00045 ( 2 hom. )
Failed GnomAD Quality Control

Consequence

HOXD13
NM_000523.4 inframe_insertion

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.191
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 -3 ACMG points.

BP3
Nonframeshift variant in repetitive region in NM_000523.4
BP6
Variant 2-176093057-G-GGGC is Benign according to our data. Variant chr2-176093057-G-GGGC is described in ClinVar as [Likely_benign]. Clinvar id is 1338819.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
HOXD13NM_000523.4 linkuse as main transcriptc.180_182dup p.Ala70dup inframe_insertion 1/2 ENST00000392539.4 NP_000514.2
HOXD13XM_011511068.3 linkuse as main transcriptc.725-1410_725-1408dup intron_variant XP_011509370.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
HOXD13ENST00000392539.4 linkuse as main transcriptc.180_182dup p.Ala70dup inframe_insertion 1/21 NM_000523.4 ENSP00000376322 P1

Frequencies

GnomAD3 genomes
AF:
0.000245
AC:
37
AN:
150788
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000194
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:
0.000194
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000400
Gnomad OTH
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.000452
AC:
551
AN:
1219006
Hom.:
2
Cov.:
30
AF XY:
0.000485
AC XY:
289
AN XY:
595800
show subpopulations
Gnomad4 AFR exome
AF:
0.0000833
Gnomad4 AMR exome
AF:
0.0000947
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000357
Gnomad4 SAS exome
AF:
0.0000199
Gnomad4 FIN exome
AF:
0.0000325
Gnomad4 NFE exome
AF:
0.000527
Gnomad4 OTH exome
AF:
0.000300
GnomAD4 genome
AF:
0.000245
AC:
37
AN:
150896
Hom.:
0
Cov.:
33
AF XY:
0.000217
AC XY:
16
AN XY:
73668
show subpopulations
Gnomad4 AFR
AF:
0.000193
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.000194
Gnomad4 NFE
AF:
0.000400
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.000196

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Brachydactyly-syndactyly syndrome Benign:1
Likely benign, criteria provided, single submitterclinical testingDaryl Scott Lab, Baylor College of MedicineJan 27, 2022- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

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: rs3832095; hg19: chr2-176957785; API