rs6745764

Variant names:

• chr2-176109394-G-A
• rs6745764
• ENST00000498438.1:n.899G>A

Your query was ambiguous. Multiple possible variants found:

• chr2-176109394-G-A
• chr2-176109394-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000498438.1(HOXD11):​n.899G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.222 in 445,660 control chromosomes in the GnomAD database, including 11,590 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.25 (4852 hom., cov: 33)
  • Exomes 𝑓: 0.21 (6738 hom.)
• Consequence: HOXD11 ENST00000498438.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.535
• Publications: 8 publications found

Genes affected

HOXD11 (HGNC:5134): (homeobox D11) 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. The product of the mouse Hoxd11 gene plays a role in forelimb morphogenesis. [provided by RefSeq, Jul 2008]

HOXD10 (HGNC:5133): (homeobox D10) This gene is a member of the Abd-B homeobox family and encodes a protein with a homeobox DNA-binding domain. It is included in a cluster of homeobox D genes located on chromosome 2. The encoded nuclear protein functions as a sequence-specific transcription factor that is expressed in the developing limb buds and is involved in differentiation and limb development. Mutations in this gene have been associated with Wilm's tumor and congenital vertical talus (also known as "rocker-bottom foot" deformity or congenital convex pes valgus) and/or a foot deformity resembling that seen in Charcot-Marie-Tooth disease. [provided by RefSeq, Jul 2008]

HOXD10 Gene-Disease associations (from GenCC):

• congenital vertical talus

  Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.318 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000498438.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HOXD11	NM_021192.3	MANE Select	c.*252G>A		3_prime_UTR	Exon 2 of 2	NP_067015.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HOXD11	ENST00000498438.1	TSL:1	n.899G>A		non_coding_transcript_exon	Exon 2 of 2
	HOXD11	ENST00000249504.7	TSL:3 MANE Select	c.*252G>A		3_prime_UTR	Exon 2 of 2	ENSP00000249504.5
	HOXD10	ENST00000490088.2	TSL:2	n.569+36G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.246 AC: 37394 AN: 152042 Hom.: 4832 Cov.: 33

Gnomad AFR AF: 0.323

Gnomad AMI AF: 0.0866

Gnomad AMR AF: 0.219

Gnomad ASJ AF: 0.224

Gnomad EAS AF: 0.209

Gnomad SAS AF: 0.162

Gnomad FIN AF: 0.234

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.220

Gnomad OTH AF: 0.222

GnomAD4 exome AF: 0.210 AC: 61657 AN: 293500 Hom.: 6738 Cov.: 0 AF XY: 0.209 AC XY: 31554 AN XY: 151090

African (AFR) AF: 0.319 AC: 3059 AN: 9594

American (AMR) AF: 0.203 AC: 2164 AN: 10680

Ashkenazi Jewish (ASJ) AF: 0.216 AC: 2234 AN: 10342

East Asian (EAS) AF: 0.187 AC: 4059 AN: 21688

South Asian (SAS) AF: 0.158 AC: 4428 AN: 28000

European-Finnish (FIN) AF: 0.231 AC: 3397 AN: 14680

Middle Eastern (MID) AF: 0.177 AC: 242 AN: 1368

European-Non Finnish (NFE) AF: 0.213 AC: 38181 AN: 179228

Other (OTH) AF: 0.217 AC: 3893 AN: 17920

GnomAD4 genome AF: 0.246 AC: 37454 AN: 152160 Hom.: 4852 Cov.: 33 AF XY: 0.243 AC XY: 18102 AN XY: 74394

African (AFR) AF: 0.323 AC: 13401 AN: 41480

American (AMR) AF: 0.218 AC: 3338 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.224 AC: 776 AN: 3466

East Asian (EAS) AF: 0.209 AC: 1082 AN: 5178

South Asian (SAS) AF: 0.163 AC: 785 AN: 4828

European-Finnish (FIN) AF: 0.234 AC: 2478 AN: 10598

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.220 AC: 14990 AN: 68006

Other (OTH) AF: 0.222 AC: 468 AN: 2110

Alfa AF: 0.226 Hom.: 5149

Bravo AF: 0.247

Asia WGS AF: 0.213 AC: 741 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	8.2
DANN	Benign	0.94
PhyloP100		0.54
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6745764; hg19: chr2-176974122;