7-97006051-GGCAGCAGCAGCAGCAGCAGCA-GGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCA

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-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]

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
DLX6NM_005222.4 linkc.87_98dupGCAGCAGCAGCA p.Gln30_Gln33dup disruptive_inframe_insertion Exon 1 of 3 ENST00000518156.3 NP_005213.3 P56179-3
DLX6-AS1NR_015448.1 linkn.141+7862_141+7873dupTGCTGCTGCTGC intron_variant Intron 1 of 2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DLX6ENST00000518156.3 linkc.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:
4
AN:
150048
Hom.:
0
Cov.:
29
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:
16
AN:
1432006
Hom.:
0
Cov.:
34
AF XY:
0.0000113
AC XY:
8
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:
4
AN:
150048
Hom.:
0
Cov.:
29
AF XY:
0.0000273
AC XY:
2
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.

Other links and lift over

dbSNP: rs530625473; hg19: chr7-96635363; API