chr7-97022094-A-G

Variant names:

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

Variant summary

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

The NM_005221.6(DLX5):​c.540+91T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.956 in 1,514,922 control chromosomes in the GnomAD database, including 691,946 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.96 (70718 hom., cov: 33)
  • Exomes 𝑓: 0.95 (621228 hom.)
• Consequence: DLX5 NM_005221.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 7-97022094-A-G is Benign according to our data. Variant chr7-97022094-A-G is described in ClinVar as Benign. ClinVar VariationId is 1241509.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.983 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005221.6. 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>C		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>C		intron	N/A	ENSP00000498116.1
	DLX5	ENST00000486603.2	TSL:2	c.*55T>C		3_prime_UTR	Exon 2 of 2	ENSP00000475008.1
	ENSG00000296253	ENST00000737644.1		n.803A>G		non_coding_transcript_exon	Exon 4 of 4

Frequencies

GnomAD3 genomes AF: 0.963 AC: 146601 AN: 152184 Hom.: 70657 Cov.: 33

Gnomad AFR AF: 0.991

Gnomad AMI AF: 0.943

Gnomad AMR AF: 0.982

Gnomad ASJ AF: 0.944

Gnomad EAS AF: 0.995

Gnomad SAS AF: 0.975

Gnomad FIN AF: 0.928

Gnomad MID AF: 0.991

Gnomad NFE AF: 0.945

Gnomad OTH AF: 0.968

GnomAD4 exome AF: 0.955 AC: 1300903 AN: 1362620 Hom.: 621228 Cov.: 21 AF XY: 0.955 AC XY: 652217 AN XY: 682952

African (AFR) AF: 0.994 AC: 31433 AN: 31636

American (AMR) AF: 0.984 AC: 43743 AN: 44476

Ashkenazi Jewish (ASJ) AF: 0.945 AC: 24178 AN: 25584

East Asian (EAS) AF: 0.997 AC: 39116 AN: 39248

South Asian (SAS) AF: 0.969 AC: 81896 AN: 84498

European-Finnish (FIN) AF: 0.928 AC: 43085 AN: 46412

Middle Eastern (MID) AF: 0.960 AC: 4482 AN: 4670

European-Non Finnish (NFE) AF: 0.951 AC: 978266 AN: 1029004

Other (OTH) AF: 0.958 AC: 54704 AN: 57092

GnomAD4 genome AF: 0.963 AC: 146721 AN: 152302 Hom.: 70718 Cov.: 33 AF XY: 0.963 AC XY: 71720 AN XY: 74460

African (AFR) AF: 0.991 AC: 41223 AN: 41580

American (AMR) AF: 0.982 AC: 15033 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.944 AC: 3275 AN: 3468

East Asian (EAS) AF: 0.995 AC: 5123 AN: 5150

South Asian (SAS) AF: 0.975 AC: 4705 AN: 4824

European-Finnish (FIN) AF: 0.928 AC: 9854 AN: 10618

Middle Eastern (MID) AF: 0.990 AC: 291 AN: 294

European-Non Finnish (NFE) AF: 0.945 AC: 64307 AN: 68032

Other (OTH) AF: 0.969 AC: 2050 AN: 2116

Alfa AF: 0.957 Hom.: 102999

Bravo AF: 0.969

Asia WGS AF: 0.988 AC: 3435 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	7.6
DANN	Benign	0.32
PhyloP100		-0.011
Mutation Taster		=8/92	disease causing

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;