Variant rs767527649 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP3BP6BS1

The NM_000523.4(HOXD13):c.106_108delGCG(p.Ala36del) variant causes a conservative 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 conservative_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]

HOXD13 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 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].

BS1

Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.0000835 (100/1198228) while in subpopulation SAS AF= 0.000583 (29/49738). AF 95% confidence interval is 0.000416. There are 0 homozygotes in gnomad4_exome. There are 59 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HOXD13	NM_000523.4 link	c.106_108delGCG	p.Ala36del	conservative_inframe_deletion	Exon 1 of 2	ENST00000392539.4	NP_000514.2	P35453
HOXD13	XM_011511068.3 link	c.725-1484_725-1482delGCG		intron_variant	Intron 1 of 1		XP_011509370.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HOXD13	ENST00000392539.4 link	c.106_108delGCG	p.Ala36del	conservative_inframe_deletion	Exon 1 of 2	1	NM_000523.4	ENSP00000376322.3		P35453

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

150896

Hom.:

Cov.:

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:

AN:

43376

Hom.:

AF XY:

0.000412

AC XY:

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.:

AF XY:

0.000101

AC XY:

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:

AN:

150896

Hom.:

Cov.:

AF XY:

0.00

AC XY:

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

May 31, 2022

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This 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.

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