rs1207733

Variant names:

• chr7-97022094-A-C
• rs1207733
• NM_005221.6:c.540+91T>G

Your query was ambiguous. Multiple possible variants found:

• chr7-97022094-A-C
• chr7-97022094-A-G
• chr7-97022094-A-T

Variant summary

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

The ENST00000648378.1(DLX5):​c.540+91T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 33)
• Consequence: DLX5 ENST00000648378.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0110
• Publications: 8 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).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000648378.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLX5	NM_005221.6	MANE Select	c.540+91T>G		intron	N/A	NP_005212.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLX5	ENST00000648378.1	MANE Select	c.540+91T>G		intron	N/A	ENSP00000498116.1
	ENSG00000296253	ENST00000737644.1		n.803A>C		non_coding_transcript_exon	Exon 4 of 4
	DLX5	ENST00000486603.2	TSL:2	c.*55T>G		3_prime_UTR	Exon 2 of 2	ENSP00000475008.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 21

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.4
DANN	Benign	0.38
PhyloP100		-0.011

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: rs1207733; hg19: chr7-96651406;