7-97021958-G-A

Position:

• chr7-97021958-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_005221.6(DLX5):​c.540+227C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0244 in 618,188 control chromosomes in the GnomAD database, including 277 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.021 (74 hom., cov: 33)
  • Exomes 𝑓: 0.025 (203 hom.)
• Consequence: DLX5 NM_005221.6 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0800

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=-0.81).
• BP6: Variant 7-97021958-G-A is Benign according to our data. Variant chr7-97021958-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1186365.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0213 (3247/152360) while in subpopulation NFE AF= 0.0301 (2048/68038). AF 95% confidence interval is 0.029. There are 74 homozygotes in gnomad4. There are 1558 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 74 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DLX5	NM_005221.6	c.540+227C>T		intron_variant		ENST00000648378.1	NP_005212.1
DLX5	XM_005250185.4	c.156+227C>T		intron_variant			XP_005250242.1
DLX5	XM_017011803.2	c.156+227C>T		intron_variant			XP_016867292.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DLX5	ENST00000648378.1	c.540+227C>T		intron_variant			NM_005221.6	ENSP00000498116	P1
DLX5	ENST00000493764.1	n.662+227C>T		intron_variant, non_coding_transcript_variant		5
DLX5	ENST00000486603.2			downstream_gene_variant		2		ENSP00000475008

Frequencies

GnomAD3 genomes AF: 0.0213 AC: 3249 AN: 152242 Hom.: 75 Cov.: 33

Gnomad AFR AF: 0.00521

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.0202

Gnomad ASJ AF: 0.0662

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00269

Gnomad FIN AF: 0.0250

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0301

Gnomad OTH AF: 0.0287

GnomAD4 exome AF: 0.0254 AC: 11815 AN: 465828 Hom.: 203 Cov.: 5 AF XY: 0.0246 AC XY: 6007 AN XY: 244596

Gnomad4 AFR exome AF: 0.00524

Gnomad4 AMR exome AF: 0.0211

Gnomad4 ASJ exome AF: 0.0670

Gnomad4 EAS exome AF: 0.0000320

Gnomad4 SAS exome AF: 0.00464

Gnomad4 FIN exome AF: 0.0289

Gnomad4 NFE exome AF: 0.0299

Gnomad4 OTH exome AF: 0.0300

GnomAD4 genome AF: 0.0213 AC: 3247 AN: 152360 Hom.: 74 Cov.: 33 AF XY: 0.0209 AC XY: 1558 AN XY: 74506

Gnomad4 AFR AF: 0.00519

Gnomad4 AMR AF: 0.0202

Gnomad4 ASJ AF: 0.0662

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00269

Gnomad4 FIN AF: 0.0250

Gnomad4 NFE AF: 0.0301

Gnomad4 OTH AF: 0.0284

Alfa AF: 0.0261 Hom.: 10

Bravo AF: 0.0209

Asia WGS AF: 0.00173 AC: 8 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 09, 2018	- -
Likely 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	-0.81
CADD	Benign	1.6
DANN	Benign	0.93

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: rs116853924; hg19: chr7-96651270;