rs9769385

Positions:

• chr7-97022673-G-A

Variant summary

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

The NM_005221.6(DLX5):​c.356-304C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0521 in 903,244 control chromosomes in the GnomAD database, including 1,406 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.060 (354 hom., cov: 32)
  • Exomes 𝑓: 0.050 (1052 hom.)
• Consequence: DLX5 NM_005221.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.138

Genes affected

DLX5 (HGNC:2918): (distal-less homeobox 5) This gene encodes a member of a homeobox transcription factor gene family similiar to the Drosophila distal-less gene. The encoded protein may play a role in bone development and fracture healing. Mutation in this gene, which is located in a tail-to-tail configuration with another member of the family on the long arm of chromosome 7, may be associated with split-hand/split-foot malformation. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 7-97022673-G-A is Benign according to our data. Variant chr7-97022673-G-A is described in ClinVar as [Benign]. Clinvar id is 1235960.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0831 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DLX5	NM_005221.6	c.356-304C>T		intron_variant		ENST00000648378.1	NP_005212.1
DLX5	XM_005250185.4			upstream_gene_variant			XP_005250242.1
DLX5	XM_017011803.2			upstream_gene_variant			XP_016867292.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DLX5	ENST00000648378.1	c.356-304C>T		intron_variant			NM_005221.6	ENSP00000498116	P1
DLX5	ENST00000486603.2	c.356-304C>T		intron_variant		2		ENSP00000475008
DLX5	ENST00000493764.1	n.560-386C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0601 AC: 9138 AN: 152140 Hom.: 355 Cov.: 32

Gnomad AFR AF: 0.0855

Gnomad AMI AF: 0.120

Gnomad AMR AF: 0.0469

Gnomad ASJ AF: 0.0913

Gnomad EAS AF: 0.0306

Gnomad SAS AF: 0.0795

Gnomad FIN AF: 0.0352

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0496

Gnomad OTH AF: 0.0712

GnomAD4 exome AF: 0.0504 AC: 37873 AN: 750986 Hom.: 1052 AF XY: 0.0507 AC XY: 17688 AN XY: 349086

Gnomad4 AFR exome AF: 0.0907

Gnomad4 AMR exome AF: 0.0356

Gnomad4 ASJ exome AF: 0.0954

Gnomad4 EAS exome AF: 0.0277

Gnomad4 SAS exome AF: 0.0780

Gnomad4 FIN exome AF: 0.0269

Gnomad4 NFE exome AF: 0.0486

Gnomad4 OTH exome AF: 0.0571

GnomAD4 genome AF: 0.0601 AC: 9150 AN: 152258 Hom.: 354 Cov.: 32 AF XY: 0.0599 AC XY: 4461 AN XY: 74444

Gnomad4 AFR AF: 0.0854

Gnomad4 AMR AF: 0.0468

Gnomad4 ASJ AF: 0.0913

Gnomad4 EAS AF: 0.0307

Gnomad4 SAS AF: 0.0800

Gnomad4 FIN AF: 0.0352

Gnomad4 NFE AF: 0.0496

Gnomad4 OTH AF: 0.0728

Alfa AF: 0.0551 Hom.: 348

Bravo AF: 0.0626

Asia WGS AF: 0.0560 AC: 195 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

Nov 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.2
DANN	Benign	0.82

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: rs9769385; hg19: chr7-96651985;