chr2-176092982-T-TGGCGGC

Variant names:

• chr2-176092982-T-TGGCGGC
• rs767527649
• NM_000523.4:c.103_108dupGCGGCG

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP3

The NM_000523.4(HOXD13):​c.103_108dupGCGGCG​(p.Ala35_Ala36dup) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000548 in 1,349,728 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00013 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000045 (0 hom.)
• Consequence: HOXD13 NM_000523.4 conservative_inframe_insertion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.870

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 -1 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_000523.4

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HOXD13	NM_000523.4	c.103_108dupGCGGCG	p.Ala35_Ala36dup	conservative_inframe_insertion	Exon 1 of 2	ENST00000392539.4	NP_000514.2
HOXD13	XM_011511068.3	c.725-1487_725-1482dupGCGGCG		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	c.103_108dupGCGGCG	p.Ala35_Ala36dup	conservative_inframe_insertion	Exon 1 of 2	1	NM_000523.4	ENSP00000376322.3

Frequencies

GnomAD3 genomes AF: 0.000133 AC: 20 AN: 150896 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000194

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000198

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000197

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000231 AC: 1 AN: 43376 Hom.: 0 AF XY: 0.0000374 AC XY: 1 AN XY: 26720

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000178

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000450 AC: 54 AN: 1198832 Hom.: 0 Cov.: 30 AF XY: 0.0000460 AC XY: 27 AN XY: 586550

Gnomad4 AFR exome AF: 0.000126

Gnomad4 AMR exome AF: 0.000272

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000777

Gnomad4 SAS exome AF: 0.0000200

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000385

Gnomad4 OTH exome AF: 0.000124

GnomAD4 genome AF: 0.000133 AC: 20 AN: 150896 Hom.: 0 Cov.: 33 AF XY: 0.000136 AC XY: 10 AN XY: 73650

Gnomad4 AFR AF: 0.000194

Gnomad4 AMR AF: 0.000198

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000197

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000118

Gnomad4 OTH AF: 0.00

Bravo AF: 0.000219

ClinVar

Not reported in ClinVar

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: rs767527649; hg19: chr2-176957710;