7-97006051-GGCAGCAGCAGCAGCAGCAGCA-GGCAGCAGCAGCAGCAGCAGCAGCAGCAGCA

Variant summary

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

The NM_005222.4(DLX6):​c.90_98dupGCAGCAGCA​(p.Gln31_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 0.000173 in 150,048 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00017 ( 0 hom., cov: 29)
Exomes 𝑓: 0.00013 ( 0 hom. )
Failed GnomAD Quality Control

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]

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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 GnomAd4 at 26 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DLX6NM_005222.4 linkc.90_98dupGCAGCAGCA p.Gln31_Gln33dup disruptive_inframe_insertion Exon 1 of 3 ENST00000518156.3 NP_005213.3 P56179-3
DLX6-AS1NR_015448.1 linkn.141+7865_141+7873dupTGCTGCTGC intron_variant Intron 1 of 2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DLX6ENST00000518156.3 linkc.90_98dupGCAGCAGCA p.Gln31_Gln33dup disruptive_inframe_insertion Exon 1 of 3 1 NM_005222.4 ENSP00000428480.2 P56179-3

Frequencies

GnomAD3 genomes
AF:
0.000173
AC:
26
AN:
150048
Hom.:
0
Cov.:
29
show subpopulations
Gnomad AFR
AF:
0.0000977
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000663
Gnomad ASJ
AF:
0.000290
Gnomad EAS
AF:
0.000197
Gnomad SAS
AF:
0.000210
Gnomad FIN
AF:
0.000397
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000208
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000844
AC:
16
AN:
189612
Hom.:
0
AF XY:
0.0000679
AC XY:
7
AN XY:
103156
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000350
Gnomad ASJ exome
AF:
0.000111
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000806
Gnomad FIN exome
AF:
0.000352
Gnomad NFE exome
AF:
0.0000492
Gnomad OTH exome
AF:
0.000408
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.000125
AC:
179
AN:
1431982
Hom.:
0
Cov.:
34
AF XY:
0.000128
AC XY:
91
AN XY:
710106
show subpopulations
Gnomad4 AFR exome
AF:
0.0000305
Gnomad4 AMR exome
AF:
0.0000243
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000523
Gnomad4 SAS exome
AF:
0.0000976
Gnomad4 FIN exome
AF:
0.000160
Gnomad4 NFE exome
AF:
0.000126
Gnomad4 OTH exome
AF:
0.000220
GnomAD4 genome
AF:
0.000173
AC:
26
AN:
150048
Hom.:
0
Cov.:
29
AF XY:
0.000123
AC XY:
9
AN XY:
73220
show subpopulations
Gnomad4 AFR
AF:
0.0000977
Gnomad4 AMR
AF:
0.0000663
Gnomad4 ASJ
AF:
0.000290
Gnomad4 EAS
AF:
0.000197
Gnomad4 SAS
AF:
0.000210
Gnomad4 FIN
AF:
0.000397
Gnomad4 NFE
AF:
0.000208
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
Dec 09, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This variant, c.90_98dup, results in the insertion of 3 amino acid(s) of the DLX6 protein (p.Gln42_Gln44dup), but otherwise preserves the integrity of the reading frame. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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. -

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