Variant chr7-97021958-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

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

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0800

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 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_single_submitter, 1 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	Effect	MANE
DLX5	NM_005221.6 linkuse as main transcript	c.540+227C>T	intron_variant	ENST00000648378.1
DLX5	XM_005250185.4 linkuse as main transcript	c.156+227C>T	intron_variant
DLX5	XM_017011803.2 linkuse as main transcript	c.156+227C>T	intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
DLX5	ENST00000648378.1 linkuse as main transcript	c.540+227C>T	intron_variant		NM_005221.6	P1	P56178-1
DLX5	ENST00000493764.1 linkuse as main transcript	n.662+227C>T	intron_variant, non_coding_transcript_variant	5
DLX5	ENST00000486603.2 linkuse as main transcript		downstream_gene_variant	2			P56178-2

Frequencies

GnomAD3 genomes

AF:

0.0213

AC:

3249

AN:

152242

Hom.:

Cov.:

show subpopulations

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.:

AF XY:

0.0246

AC XY:

6007

AN XY:

244596

show subpopulations

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.:

Cov.:

AF XY:

0.0209

AC XY:

1558

AN XY:

74506

show subpopulations

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.:

Bravo

AF:

0.0209

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 09, 2018

- -

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over