chr2-176092852-G-C

Variant names:

• chr2-176092852-G-C
• rs144577020
• NM_000523.4:c.-39G>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000523.4(HOXD13):​c.-39G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0104 in 1,180,036 control chromosomes in the GnomAD database, including 873 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.046 (543 hom., cov: 33)
  • Exomes 𝑓: 0.0052 (330 hom.)
• Consequence: HOXD13 NM_000523.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.115

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

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 2-176092852-G-C is Benign according to our data. Variant chr2-176092852-G-C is described in ClinVar as [Benign]. Clinvar id is 1228320.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.154 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HOXD13	NM_000523.4	c.-39G>C		5_prime_UTR_variant	Exon 1 of 2	ENST00000392539.4	NP_000514.2
HOXD13	XM_011511068.3	c.725-1628G>C		intron_variant	Intron 1 of 1		XP_011509370.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HOXD13	ENST00000392539	c.-39G>C		5_prime_UTR_variant	Exon 1 of 2	1	NM_000523.4	ENSP00000376322.3

Frequencies

GnomAD3 genomes AF: 0.0460 AC: 6980 AN: 151724 Hom.: 542 Cov.: 33

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0209

Gnomad ASJ AF: 0.000577

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.000381

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.00130

Gnomad OTH AF: 0.0340

GnomAD2 exomes AF: 0.00689 AC: 17 AN: 2466 AF XY: 0.00150

Gnomad AFR exome AF: 0.147

Gnomad AMR exome AF: 0.0455

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000462

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00516 AC: 5309 AN: 1028202 Hom.: 330 Cov.: 18 AF XY: 0.00483 AC XY: 2360 AN XY: 489096

Gnomad4 AFR exome AF: 0.166 AC: 3505 AN: 21134

Gnomad4 AMR exome AF: 0.0120 AC: 88 AN: 7320

Gnomad4 ASJ exome AF: 0.000471 AC: 6 AN: 12750

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 24500

Gnomad4 SAS exome AF: 0.000206 AC: 4 AN: 19444

Gnomad4 FIN exome AF: 0.000588 AC: 12 AN: 20392

Gnomad4 NFE exome AF: 0.00137 AC: 1202 AN: 879286

Gnomad4 Remaining exome AF: 0.0116 AC: 472 AN: 40642

GnomAD4 genome AF: 0.0461 AC: 7002 AN: 151834 Hom.: 543 Cov.: 33 AF XY: 0.0448 AC XY: 3329 AN XY: 74244

Gnomad4 AFR AF: 0.157 AC: 0.157128 AN: 0.157128

Gnomad4 AMR AF: 0.0210 AC: 0.0210216 AN: 0.0210216

Gnomad4 ASJ AF: 0.000577 AC: 0.000576701 AN: 0.000576701

Gnomad4 EAS AF: 0.000195 AC: 0.000194628 AN: 0.000194628

Gnomad4 SAS AF: 0.000414 AC: 0.000414422 AN: 0.000414422

Gnomad4 FIN AF: 0.000381 AC: 0.000380807 AN: 0.000380807

Gnomad4 NFE AF: 0.00130 AC: 0.00129656 AN: 0.00129656

Gnomad4 OTH AF: 0.0336 AC: 0.0336493 AN: 0.0336493

Alfa AF: 0.00696 Hom.: 11

Bravo AF: 0.0534

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	12
DANN	Benign	0.54

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs144577020; hg19: chr2-176957580;