Variant 7-97021075-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_005221.6(DLX5):c.541-10C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00375 in 1,595,074 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0029 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0038 ( 13 hom. )

Consequence

DLX5
NM_005221.6 splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00004088

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 2.13

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant 7-97021075-G-A is Benign according to our data. Variant chr7-97021075-G-A is described in ClinVar as [Benign]. Clinvar id is 713599.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
DLX5	NM_005221.6 linkuse as main transcript	c.541-10C>T	splice_polypyrimidine_tract_variant, intron_variant	ENST00000648378.1	NP_005212.1
DLX5	XM_005250185.4 linkuse as main transcript	c.157-10C>T	splice_polypyrimidine_tract_variant, intron_variant		XP_005250242.1
DLX5	XM_017011803.2 linkuse as main transcript	c.157-10C>T	splice_polypyrimidine_tract_variant, intron_variant		XP_016867292.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DLX5	ENST00000648378.1 linkuse as main transcript	c.541-10C>T		splice_polypyrimidine_tract_variant, intron_variant			NM_005221.6	ENSP00000498116	P1	P56178-1
DLX5	ENST00000493764.1 linkuse as main transcript	n.663-10C>T		splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.00288

AC:

439

AN:

152258

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000723

Gnomad AMI

AF:

0.0822

Gnomad AMR

AF:

0.00118

Gnomad ASJ

AF:

0.00548

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000847

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00410

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.00218

AC:

521

AN:

239164

Hom.:

AF XY:

0.00212

AC XY:

274

AN XY:

129040

show subpopulations

Gnomad AFR exome

AF:

0.000880

Gnomad AMR exome

AF:

0.000972

Gnomad ASJ exome

AF:

0.00401

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000250

Gnomad FIN exome

AF:

0.00105

Gnomad NFE exome

AF:

0.00369

Gnomad OTH exome

AF:

0.00224

GnomAD4 exome

AF:

0.00385

AC:

5549

AN:

1442698

Hom.:

Cov.:

AF XY:

0.00378

AC XY:

2700

AN XY:

714736

show subpopulations

Gnomad4 AFR exome

AF:

0.000784

Gnomad4 AMR exome

AF:

0.00102

Gnomad4 ASJ exome

AF:

0.00387

Gnomad4 EAS exome

AF:

0.0000762

Gnomad4 SAS exome

AF:

0.000131

Gnomad4 FIN exome

AF:

0.00146

Gnomad4 NFE exome

AF:

0.00466

Gnomad4 OTH exome

AF:

0.00253

GnomAD4 genome

AF:

0.00288

AC:

439

AN:

152376

Hom.:

Cov.:

AF XY:

0.00267

AC XY:

199

AN XY:

74530

show subpopulations

Gnomad4 AFR

AF:

0.000721

Gnomad4 AMR

AF:

0.00118

Gnomad4 ASJ

AF:

0.00548

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000847

Gnomad4 NFE

AF:

0.00410

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.00326

Hom.:

Bravo

AF:

0.00310

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

DLX5-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 24, 2024

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Nov 28, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Benign

0.89

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000041

dbscSNV1_RF

Benign

0.018

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