2-176093057-G-GGGC

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 0P and 3B. BP3 BP6_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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.191

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]

ACMG classification

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	UniProt
HOXD13	NM_000523.4	c.180_182dup	p.Ala70dup	inframe_insertion	1/2	ENST00000392539.4
HOXD13	XM_011511068.3	c.725-1410_725-1408dup		intron_variant

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.000245 AC: 37 AN: 150788 Hom.: 0 Cov.: 33

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

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

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

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

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3832095; hg19: chr2-176957785;