Genetic Variant DLX6:p.Gln34_Gln39del (chr7-97006058-GCAGCAGCAGCAGCAGCAA-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_116delACAGCAGCAGCAGCAGCA(p.Gln34_Gln39del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.000208 in 1,577,562 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00019 ( 0 hom., cov: 29)

Exomes 𝑓: 0.00021 ( 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: 4.42

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 28 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLX6	NM_005222.4 link	c.99_116delACAGCAGCAGCAGCAGCA	p.Gln34_Gln39del	disruptive_inframe_deletion	Exon 1 of 3	ENST00000518156.3	NP_005213.3	P56179-3
DLX6-AS1	NR_015448.1 link	n.141+7849_141+7866delTTGCTGCTGCTGCTGCTG		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_116delACAGCAGCAGCAGCAGCA	p.Gln34_Gln39del	disruptive_inframe_deletion	Exon 1 of 3	1	NM_005222.4	ENSP00000428480.2		P56179-3

Frequencies

GnomAD3 genomes

AF:

0.000185

AC:

AN:

151038

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000218

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000329

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000200

Gnomad SAS

AF:

0.000418

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000148

Gnomad OTH

AF:

0.000482

GnomAD3 exomes

AF:

0.000171

AC:

AN:

187494

Hom.:

AF XY:

0.000166

AC XY:

AN XY:

102148

show subpopulations

Gnomad AFR exome

AF:

0.000206

Gnomad AMR exome

AF:

0.000493

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000373

Gnomad SAS exome

AF:

0.0000799

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000101

Gnomad OTH exome

AF:

0.000202

GnomAD4 exome

AF:

0.000210

AC:

300

AN:

1426416

Hom.:

AF XY:

0.000219

AC XY:

155

AN XY:

706652

show subpopulations

Gnomad4 AFR exome

AF:

0.000214

Gnomad4 AMR exome

AF:

0.000452

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000133

Gnomad4 SAS exome

AF:

0.000245

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000218

Gnomad4 OTH exome

AF:

0.000152

GnomAD4 genome

AF:

0.000185

AC:

AN:

151146

Hom.:

Cov.:

AF XY:

0.000217

AC XY:

AN XY:

73872

show subpopulations

Gnomad4 AFR

AF:

0.000218

Gnomad4 AMR

AF:

0.000329

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000200

Gnomad4 SAS

AF:

0.000418

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000148

Gnomad4 OTH

AF:

0.000477

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Aug 04, 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. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. ClinVar contains an entry for this variant (Variation ID: 1365121). 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.99_116del, results in the deletion of 6 amino acid(s) of the DLX6 protein (p.Gln39_Gln44del), but otherwise preserves the integrity of the reading frame. -

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