7-97022094-A-G

Position:

• chr7-97022094-A-G

Variant summary

Our verdict is Benign. Variant got -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

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 -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DLX5	NM_005221.6	c.540+91T>C		intron_variant		ENST00000648378.1	NP_005212.1
DLX5	XM_005250185.4	c.156+91T>C		intron_variant			XP_005250242.1
DLX5	XM_017011803.2	c.156+91T>C		intron_variant			XP_016867292.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DLX5	ENST00000648378.1	c.540+91T>C		intron_variant			NM_005221.6	ENSP00000498116	P1
DLX5	ENST00000486603.2	c.*55T>C		3_prime_UTR_variant	2/2	2		ENSP00000475008
DLX5	ENST00000493764.1	n.662+91T>C		intron_variant, non_coding_transcript_variant		5

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

Gnomad4 AFR exome AF: 0.994

Gnomad4 AMR exome AF: 0.984

Gnomad4 ASJ exome AF: 0.945

Gnomad4 EAS exome AF: 0.997

Gnomad4 SAS exome AF: 0.969

Gnomad4 FIN exome AF: 0.928

Gnomad4 NFE exome AF: 0.951

Gnomad4 OTH exome AF: 0.958

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

Gnomad4 AFR AF: 0.991

Gnomad4 AMR AF: 0.982

Gnomad4 ASJ AF: 0.944

Gnomad4 EAS AF: 0.995

Gnomad4 SAS AF: 0.975

Gnomad4 FIN AF: 0.928

Gnomad4 NFE AF: 0.945

Gnomad4 OTH AF: 0.969

Alfa AF: 0.954 Hom.: 70011

Bravo AF: 0.969

Asia WGS AF: 0.988 AC: 3435 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 16, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	7.6
DANN	Benign	0.32

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: rs1207733; hg19: chr7-96651406;