rs9769385

Variant names:

• chr7-97022673-G-A
• rs9769385
• NM_005221.6:c.356-304C>T

Your query was ambiguous. Multiple possible variants found:

• chr7-97022673-G-A
• chr7-97022673-G-C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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]

DLX5 Gene-Disease associations (from GenCC):

• split hand-foot malformation 1 with sensorineural hearing loss

  Inheritance: AR, AD Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Orphanet, G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• split hand-foot malformation 1

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
• split hand-foot malformation

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000296253 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
DLX5	NM_005221.6	c.356-304C>T		intron_variant	Intron 1 of 2	ENST00000648378.1	NP_005212.1
DLX5	XM_005250185.4	c.-170C>T		upstream_gene_variant			XP_005250242.1
DLX5	XM_017011803.2	c.-242C>T		upstream_gene_variant			XP_016867292.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DLX5	ENST00000648378.1	c.356-304C>T		intron_variant	Intron 1 of 2		NM_005221.6	ENSP00000498116.1
DLX5	ENST00000486603.2	c.356-304C>T		intron_variant	Intron 1 of 1	2		ENSP00000475008.1
DLX5	ENST00000493764.1	n.560-386C>T		intron_variant	Intron 1 of 2	5
ENSG00000296253	ENST00000737642.1	n.109+1824G>A		intron_variant	Intron 1 of 3

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

African (AFR) AF: 0.0907 AC: 1281 AN: 14120

American (AMR) AF: 0.0356 AC: 32 AN: 898

Ashkenazi Jewish (ASJ) AF: 0.0954 AC: 443 AN: 4642

East Asian (EAS) AF: 0.0277 AC: 89 AN: 3212

South Asian (SAS) AF: 0.0780 AC: 1151 AN: 14752

European-Finnish (FIN) AF: 0.0269 AC: 7 AN: 260

Middle Eastern (MID) AF: 0.0595 AC: 89 AN: 1496

European-Non Finnish (NFE) AF: 0.0486 AC: 33382 AN: 687118

Other (OTH) AF: 0.0571 AC: 1399 AN: 24488

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

African (AFR) AF: 0.0854 AC: 3549 AN: 41536

American (AMR) AF: 0.0468 AC: 716 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0913 AC: 317 AN: 3472

East Asian (EAS) AF: 0.0307 AC: 159 AN: 5180

South Asian (SAS) AF: 0.0800 AC: 385 AN: 4814

European-Finnish (FIN) AF: 0.0352 AC: 373 AN: 10602

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0496 AC: 3373 AN: 68030

Other (OTH) AF: 0.0728 AC: 154 AN: 2114

Alfa AF: 0.0558 Hom.: 459

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

Nov 10, 2018

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	-0.81
CADD	Benign	4.2
DANN	Benign	0.82
PhyloP100		-0.14
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: rs9769385; hg19: chr7-96651985;