Variant 2-176093057-GGGCGGCGGCGGC-GGGCGGCGGCGGCGGC details in Genebe, Genetics Data Aggregator

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]

HOXD13 links:

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
HOXD13	NM_000523.4 linkuse as main transcript	c.180_182dup	p.Ala70dup	inframe_insertion	1/2	ENST00000392539.4	NP_000514.2
HOXD13	XM_011511068.3 linkuse as main transcript	c.725-1410_725-1408dup		intron_variant			XP_011509370.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HOXD13	ENST00000392539.4 linkuse as main transcript	c.180_182dup	p.Ala70dup	inframe_insertion	1/2	1	NM_000523.4	ENSP00000376322	P1

Frequencies

GnomAD3 genomes

AF:

0.000245

AC:

AN:

150788

Hom.:

Cov.:

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.:

Cov.:

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:

AN:

150896

Hom.:

Cov.:

AF XY:

0.000217

AC XY:

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 submitter

clinical testing

Daryl Scott Lab, Baylor College of Medicine

Jan 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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over