7-97006052-G-GCAGCAGCAGCAGCAGCAGCAGCAACAGCAGCAGCAGCAGCAGCAGCAACAGCAGCAGCAGCAGCAGCAGCAA

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP3

The NM_005222.4(DLX6):​c.128_129insGCAGCAGCAGCAGCAGCAACAGCAGCAGCAGCAGCAGCAGCAACAGCAGCAGCAGCAGCAGCAGCAACAGCA​(p.Gln43_Gln44insGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGln) variant causes a disruptive inframe insertion change. The variant allele was found at a frequency of 0.000000723 in 1,382,522 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. Q43Q) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 29)
Exomes 𝑓: 7.2e-7 ( 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: 4.05
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 was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP3
Nonframeshift variant in repetitive region in NM_005222.4

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DLX6NM_005222.4 linkc.128_129insGCAGCAGCAGCAGCAGCAACAGCAGCAGCAGCAGCAGCAGCAACAGCAGCAGCAGCAGCAGCAGCAACAGCA p.Gln43_Gln44insGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGln disruptive_inframe_insertion Exon 1 of 3 ENST00000518156.3 NP_005213.3 P56179-3
DLX6-AS1NR_015448.1 linkn.141+7872_141+7873insTTGCTGCTGCTGCTGCTGCTGCTGTTGCTGCTGCTGCTGCTGCTGCTGTTGCTGCTGCTGCTGCTGCTGCTG intron_variant Intron 1 of 2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DLX6ENST00000518156.3 linkc.128_129insGCAGCAGCAGCAGCAGCAACAGCAGCAGCAGCAGCAGCAGCAACAGCAGCAGCAGCAGCAGCAGCAACAGCA p.Gln43_Gln44insGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGln disruptive_inframe_insertion Exon 1 of 3 1 NM_005222.4 ENSP00000428480.2 P56179-3

Frequencies

GnomAD3 genomes
Cov.:
29
GnomAD4 exome
AF:
7.23e-7
AC:
1
AN:
1382522
Hom.:
0
Cov.:
34
AF XY:
0.00
AC XY:
0
AN XY:
683696
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
31010
American (AMR)
AF:
0.00
AC:
0
AN:
36900
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
24598
East Asian (EAS)
AF:
0.00
AC:
0
AN:
35082
South Asian (SAS)
AF:
0.00
AC:
0
AN:
77598
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
44904
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5588
European-Non Finnish (NFE)
AF:
9.35e-7
AC:
1
AN:
1069820
Other (OTH)
AF:
0.00
AC:
0
AN:
57022
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Cov.:
29

ClinVar

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

Submissions by phenotype

not provided Uncertain:1
Jul 14, 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 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.128_129insGCAGCAGCAGCAGCAGCAACAGCAGCAGCAGCAGCAGCAGCAACAGCAGCAGCAGCAGCAGCAGCAACAGCA, results in the insertion of 24 amino acid(s) of the DLX6 protein (p.Gln44_Pro45insGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGln), 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: rs775320932; hg19: chr7-96635364; API