7-97006052-G-GCAGCAGCAGCAGCAGCAGCAGCAACAGCAGCAGCAGCAGCAGCAGCAACAGCAGCAGCAGCAGCAGCAGCAA

Variant summary

Our verdict is Uncertain significance. Variant got 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 (★).

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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 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/exons MANE Protein UniProt
DLX6NM_005222.4 linkc.128_129insGCAGCAGCAGCAGCAGCAACAGCAGCAGCAGCAGCAGCAGCAACAGCAGCAGCAGCAGCAGCAGCAACAGCA p.Gln43_Gln44insGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGln disruptive_inframe_insertion 1/3 ENST00000518156.3 NP_005213.3 P56179-3
DLX6-AS1NR_015448.1 linkn.141+7872_141+7873insTTGCTGCTGCTGCTGCTGCTGCTGTTGCTGCTGCTGCTGCTGCTGCTGTTGCTGCTGCTGCTGCTGCTGCTG intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
DLX6ENST00000518156.3 linkc.128_129insGCAGCAGCAGCAGCAGCAACAGCAGCAGCAGCAGCAGCAGCAACAGCAGCAGCAGCAGCAGCAGCAACAGCA p.Gln43_Gln44insGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGln disruptive_inframe_insertion 1/31 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
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.35e-7
Gnomad4 OTH exome
AF:
0.00
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
Uncertain significance, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJul 14, 2023In 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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-96635364; API