7-97022673-G-C

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005221.6(DLX5):​c.356-304C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000665 in 751,348 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000067 (0 hom.)
• Consequence: DLX5 NM_005221.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.138
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLX5	NM_005221.6	c.356-304C>G		intron_variant	Intron 1 of 2	ENST00000648378.1	NP_005212.1
DLX5	XM_005250185.4	c.-170C>G		upstream_gene_variant			XP_005250242.1
DLX5	XM_017011803.2	c.-242C>G		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>G		intron_variant	Intron 1 of 2		NM_005221.6	ENSP00000498116.1
DLX5	ENST00000486603.2	c.356-304C>G		intron_variant	Intron 1 of 1	2		ENSP00000475008.1
DLX5	ENST00000493764.1	n.560-386C>G		intron_variant	Intron 1 of 2	5
ENSG00000296253	ENST00000737642.1	n.109+1824G>C		intron_variant	Intron 1 of 3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000665 AC: 5 AN: 751348 Hom.: 0 AF XY: 0.0000115 AC XY: 4 AN XY: 349240

African (AFR) AF: 0.00 AC: 0 AN: 14128

American (AMR) AF: 0.00 AC: 0 AN: 900

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4644

East Asian (EAS) AF: 0.00 AC: 0 AN: 3212

South Asian (SAS) AF: 0.00 AC: 0 AN: 14782

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 260

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1496

European-Non Finnish (NFE) AF: 0.00000582 AC: 4 AN: 687430

Other (OTH) AF: 0.0000408 AC: 1 AN: 24496

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.5
DANN	Benign	0.66
PhyloP100		-0.14

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;