Variant 7-97006051-GGCAGCA-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_005222.4(DLX6):c.93_98delGCAGCA(p.Gln32_Gln33del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.000298 in 1,582,078 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00047 ( 1 hom., cov: 29)

Exomes 𝑓: 0.00028 ( 1 hom. )

Consequence

DLX6
NM_005222.4 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1B:1

Conservation

PhyloP100: 6.66

Variant links:

Genes affected

DLX6 (HGNC:2919): (distal-less homeobox 6) This gene encodes a member of a homeobox transcription factor gene family similiar to the Drosophila distal-less gene. This family is comprised of at least 6 different members that encode proteins with roles in forebrain and craniofacial development. This gene is in a tail-to-tail configuration with another member of the family on the long arm of chromosome 7. [provided by RefSeq, Jul 2008]

DLX6 links:

DLX6-AS1 (HGNC:37151): (DLX6 antisense RNA 1) Predicted to act upstream of or within positive regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

DLX6-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAd4 at 71 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DLX6	NM_005222.4 link	c.93_98delGCAGCA	p.Gln32_Gln33del	disruptive_inframe_deletion	1/3	ENST00000518156.3	NP_005213.3	P56179-3
DLX6-AS1	NR_015448.1 link	n.141+7868_141+7873delTGCTGC		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DLX6	ENST00000518156.3 link	c.93_98delGCAGCA	p.Gln32_Gln33del	disruptive_inframe_deletion	1/3	1	NM_005222.4	ENSP00000428480.2		P56179-3

Frequencies

GnomAD3 genomes

AF:

0.000473

AC:

AN:

150048

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000195

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000133

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00966

Gnomad SAS

AF:

0.000210

Gnomad FIN

AF:

0.0000993

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000134

Gnomad OTH

AF:

0.000485

GnomAD3 exomes

AF:

0.000796

AC:

151

AN:

189612

Hom.:

AF XY:

0.000650

AC XY:

AN XY:

103156

show subpopulations

Gnomad AFR exome

AF:

0.000384

Gnomad AMR exome

AF:

0.000315

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00902

Gnomad SAS exome

AF:

0.000161

Gnomad FIN exome

AF:

0.000117

Gnomad NFE exome

AF:

0.000123

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000279

AC:

400

AN:

1431934

Hom.:

AF XY:

0.000259

AC XY:

184

AN XY:

710086

show subpopulations

Gnomad4 AFR exome

AF:

0.000275

Gnomad4 AMR exome

AF:

0.000292

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00568

Gnomad4 SAS exome

AF:

0.000159

Gnomad4 FIN exome

AF:

0.0000200

Gnomad4 NFE exome

AF:

0.000118

Gnomad4 OTH exome

AF:

0.000287

GnomAD4 genome

AF:

0.000473

AC:

AN:

150144

Hom.:

Cov.:

AF XY:

0.000518

AC XY:

AN XY:

73326

show subpopulations

Gnomad4 AFR

AF:

0.000195

Gnomad4 AMR

AF:

0.000132

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00969

Gnomad4 SAS

AF:

0.000210

Gnomad4 FIN

AF:

0.0000993

Gnomad4 NFE

AF:

0.000134

Gnomad4 OTH

AF:

0.000482

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Apr 10, 2023

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant has not been reported in the literature in individuals affected with DLX6-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant, c.93_98del, results in the deletion of 2 amino acid(s) of the DLX6 protein (p.Gln43_Gln44del), but otherwise preserves the integrity of the reading frame. -

DLX6-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 11, 2020

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

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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