Genetic Variant DLX6:p.Gln34_Gln40del (chr7-97006055-GCAGCAGCAGCAGCAGCAGCAA-G) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP3BS2

The NM_005222.4(DLX6):c.99_119delACAGCAGCAGCAGCAGCAGCA(p.Gln34_Gln40del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.000166 in 1,574,834 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00017 ( 0 hom., cov: 29)

Exomes 𝑓: 0.00016 ( 0 hom. )

Consequence

DLX6
NM_005222.4 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U: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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_005222.4

BS2

High AC in GnomAd4 at 26 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLX6	NM_005222.4 link	c.99_119delACAGCAGCAGCAGCAGCAGCA	p.Gln34_Gln40del	disruptive_inframe_deletion	Exon 1 of 3	ENST00000518156.3	NP_005213.3	P56179-3
DLX6-AS1	NR_015448.1 link	n.141+7849_141+7869delTTGCTGCTGCTGCTGCTGCTG		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DLX6	ENST00000518156.3 link	c.99_119delACAGCAGCAGCAGCAGCAGCA	p.Gln34_Gln40del	disruptive_inframe_deletion	Exon 1 of 3	1	NM_005222.4	ENSP00000428480.2		P56179-3

Frequencies

GnomAD3 genomes

AF:

0.000173

AC:

AN:

150444

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000122

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000660

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000399

Gnomad SAS

AF:

0.000836

Gnomad FIN

AF:

0.0000981

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000178

Gnomad OTH

AF:

0.000484

GnomAD3 exomes

AF:

0.000159

AC:

AN:

176642

Hom.:

AF XY:

0.000177

AC XY:

AN XY:

96166

show subpopulations

Gnomad AFR exome

AF:

0.000113

Gnomad AMR exome

AF:

0.000257

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000396

Gnomad SAS exome

AF:

0.000289

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000108

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000165

AC:

235

AN:

1424288

Hom.:

AF XY:

0.000174

AC XY:

123

AN XY:

705494

show subpopulations

Gnomad4 AFR exome

AF:

0.000277

Gnomad4 AMR exome

AF:

0.000202

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000323

Gnomad4 SAS exome

AF:

0.000662

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000126

Gnomad4 OTH exome

AF:

0.000220

GnomAD4 genome

AF:

0.000173

AC:

AN:

150546

Hom.:

Cov.:

AF XY:

0.000163

AC XY:

AN XY:

73538

show subpopulations

Gnomad4 AFR

AF:

0.000122

Gnomad4 AMR

AF:

0.0000659

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000400

Gnomad4 SAS

AF:

0.000836

Gnomad4 FIN

AF:

0.0000981

Gnomad4 NFE

AF:

0.000178

Gnomad4 OTH

AF:

0.000480

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Sep 05, 2023

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. This variant, c.99_119del, results in the deletion of 7 amino acid(s) of the DLX6 protein (p.Gln38_Gln44del), but otherwise preserves the integrity of the reading frame. 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 has not been reported in the literature in individuals affected with DLX6-related conditions. ClinVar contains an entry for this variant (Variation ID: 1498979). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. -

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