7-97006051-GGCAGCAGCAGCAGCAGCAGCA-GGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCA

Variant summary

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

The NM_005222.4(DLX6):​c.84_98dupGCAGCAGCAGCAGCA​(p.Gln29_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 0.0000379 in 1,582,048 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000067 ( 0 hom., cov: 29)
Exomes 𝑓: 0.000041 ( 0 hom. )

Consequence

DLX6
NM_005222.4 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U: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 59 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DLX6NM_005222.4 linkc.84_98dupGCAGCAGCAGCAGCA p.Gln29_Gln33dup disruptive_inframe_insertion Exon 1 of 3 ENST00000518156.3 NP_005213.3 P56179-3
DLX6-AS1NR_015448.1 linkn.141+7859_141+7873dupTGCTGCTGCTGCTGC intron_variant Intron 1 of 2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DLX6ENST00000518156.3 linkc.84_98dupGCAGCAGCAGCAGCA p.Gln29_Gln33dup disruptive_inframe_insertion Exon 1 of 3 1 NM_005222.4 ENSP00000428480.2 P56179-3

Frequencies

GnomAD3 genomes
AF:
0.00000666
AC:
1
AN:
150048
Hom.:
0
Cov.:
29
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.0000148
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.0000412
AC:
59
AN:
1432000
Hom.:
0
Cov.:
34
AF XY:
0.0000465
AC XY:
33
AN XY:
710118
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000680
Gnomad4 SAS exome
AF:
0.0000122
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000282
Gnomad4 OTH exome
AF:
0.0000169
GnomAD4 genome
AF:
0.00000666
AC:
1
AN:
150048
Hom.:
0
Cov.:
29
AF XY:
0.00
AC XY:
0
AN XY:
73220
show subpopulations
Gnomad4 AFR
AF:
0.00
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:
0.0000148
Gnomad4 OTH
AF:
0.00

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Uncertain:1
Jul 15, 2022
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with DLX6-related conditions. 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.84_98dup, results in the insertion of 5 amino acid(s) of the DLX6 protein (p.Gln40_Gln44dup), 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.

Other links and lift over

dbSNP: rs530625473; hg19: chr7-96635363; API