Genetic Variant DLX6:p.Gln30_Gln33dup (chr7-97006051-G-GGCAGCAGCAGCA) – 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.87_98dupGCAGCAGCAGCA(p.Gln30_Gln33dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000126 in 1,582,054 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., cov: 29)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

DLX6
NM_005222.4 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

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

Conservation

PhyloP100: 2.11

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 -5 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_005222.4

BS2

High AC in GnomAdExome4 at 16 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLX6	NM_005222.4 link	c.87_98dupGCAGCAGCAGCA	p.Gln30_Gln33dup	disruptive_inframe_insertion	Exon 1 of 3	ENST00000518156.3	NP_005213.3	P56179-3
DLX6-AS1	NR_015448.1 link	n.141+7862_141+7873dupTGCTGCTGCTGC		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DLX6	ENST00000518156.3 link	c.87_98dupGCAGCAGCAGCA	p.Gln30_Gln33dup	disruptive_inframe_insertion	Exon 1 of 3	1	NM_005222.4	ENSP00000428480.2		P56179-3

Frequencies

GnomAD3 genomes

AF:

0.0000267

AC:

AN:

150048

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000977

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000112

AC:

AN:

1432006

Hom.:

Cov.:

AF XY:

0.0000113

AC XY:

AN XY:

710120

show subpopulations

Gnomad4 AFR exome

AF:

0.0000916

Gnomad4 AMR exome

AF:

0.0000486

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000262

Gnomad4 SAS exome

AF:

0.0000122

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000638

Gnomad4 OTH exome

AF:

0.0000338

GnomAD4 genome

AF:

0.0000267

AC:

AN:

150048

Hom.:

Cov.:

AF XY:

0.0000273

AC XY:

AN XY:

73220

show subpopulations

Gnomad4 AFR

AF:

0.0000977

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Sep 21, 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. This variant has not been reported in the literature in individuals affected with DLX6-related conditions. This variant is not present in population databases (gnomAD no frequency). This variant, c.87_98dup, results in the insertion of 4 amino acid(s) of the DLX6 protein (p.Gln41_Gln44dup), but otherwise preserves the integrity of the reading frame. -

DLX6-related disorder

Benign:1

Jul 15, 2021

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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). -

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.

7-97006051-GGCAGCAGCAGCAGCAGCAGCA-GGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCA

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