rs847194

Positions:

• chr2-176093973-A-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000523.4(HOXD13):​c.781+302A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.376 in 152,018 control chromosomes in the GnomAD database, including 14,120 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.38 (14120 hom., cov: 32)
• Consequence: HOXD13 NM_000523.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.02

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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 2-176093973-A-C is Benign according to our data. Variant chr2-176093973-A-C is described in ClinVar as [Benign]. Clinvar id is 1260461.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.703 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HOXD13	NM_000523.4	c.781+302A>C		intron_variant		ENST00000392539.4
HOXD13	XM_011511068.3	c.725-507A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HOXD13	ENST00000392539.4	c.781+302A>C		intron_variant		1	NM_000523.4	P1

Frequencies

GnomAD3 genomes AF: 0.375 AC: 57021 AN: 151900 Hom.: 14072 Cov.: 32

Gnomad AFR AF: 0.710

Gnomad AMI AF: 0.0669

Gnomad AMR AF: 0.309

Gnomad ASJ AF: 0.277

Gnomad EAS AF: 0.332

Gnomad SAS AF: 0.378

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.299

Gnomad NFE AF: 0.235

Gnomad OTH AF: 0.343

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.376 AC: 57128 AN: 152018 Hom.: 14120 Cov.: 32 AF XY: 0.371 AC XY: 27560 AN XY: 74306

Gnomad4 AFR AF: 0.710

Gnomad4 AMR AF: 0.309

Gnomad4 ASJ AF: 0.277

Gnomad4 EAS AF: 0.332

Gnomad4 SAS AF: 0.379

Gnomad4 FIN AF: 0.157

Gnomad4 NFE AF: 0.235

Gnomad4 OTH AF: 0.347

Alfa AF: 0.274 Hom.: 3560

Bravo AF: 0.399

Asia WGS AF: 0.393 AC: 1371 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 16, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.25
DANN	Benign	0.38

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

Other links and lift over

dbSNP: rs847194; hg19: chr2-176958701;