GeneBe

7-97006051-G-GGCAGCAGCAGCAGCAGCAGCAGCA

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP3

The NM_005222.4(DLX6):​c.75_98dupGCAGCAGCAGCAGCAGCAGCAGCA​(p.Gln33_Gln34insGlnGlnGlnGlnGlnGlnGlnGln) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000267 in 150,048 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. Q33Q) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., cov: 29)
Exomes 𝑓: 7.0e-7 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

DLX6
NM_005222.4 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.11

Publications

0 publications found
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 was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

BP3
Nonframeshift variant in repetitive region in NM_005222.4

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005222.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
DLX6
NM_005222.4
MANE Select
c.75_98dupGCAGCAGCAGCAGCAGCAGCAGCAp.Gln33_Gln34insGlnGlnGlnGlnGlnGlnGlnGln
disruptive_inframe_insertion
Exon 1 of 3NP_005213.3
DLX6-AS1
NR_015448.1
n.141+7850_141+7873dupTGCTGCTGCTGCTGCTGCTGCTGC
intron
N/A

Ensembl Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
DLX6
ENST00000518156.3
TSL:1 MANE Select
c.75_98dupGCAGCAGCAGCAGCAGCAGCAGCAp.Gln33_Gln34insGlnGlnGlnGlnGlnGlnGlnGln
disruptive_inframe_insertion
Exon 1 of 3ENSP00000428480.2P56179-3
DLX6-AS1
ENST00000458352.5
TSL:1
n.615+5750_615+5773dupTGCTGCTGCTGCTGCTGCTGCTGC
intron
N/A
DLX6-AS1
ENST00000430027.3
TSL:2
n.141+7850_141+7873dupTGCTGCTGCTGCTGCTGCTGCTGC
intron
N/A

Frequencies

GnomAD3 genomes
AF:
0.0000267
AC:
4
AN:
150048
Hom.:
0
Cov.:
29
show subpopulations
Gnomad AFR
AF:
0.0000244
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000133
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:
0.000485
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
6.98e-7
AC:
1
AN:
1432004
Hom.:
0
Cov.:
34
AF XY:
0.00
AC XY:
0
AN XY:
710120
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.0000305
AC:
1
AN:
32742
American (AMR)
AF:
0.00
AC:
0
AN:
41158
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25642
East Asian (EAS)
AF:
0.00
AC:
0
AN:
38222
South Asian (SAS)
AF:
0.00
AC:
0
AN:
81960
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
49986
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5722
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1097404
Other (OTH)
AF:
0.00
AC:
0
AN:
59168
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.225
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
AF:
0.0000267
AC:
4
AN:
150048
Hom.:
0
Cov.:
29
AF XY:
0.0000273
AC XY:
2
AN XY:
73220
show subpopulations
African (AFR)
AF:
0.0000244
AC:
1
AN:
40956
American (AMR)
AF:
0.000133
AC:
2
AN:
15084
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3450
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5074
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4760
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10066
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
304
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
67382
Other (OTH)
AF:
0.000485
AC:
1
AN:
2060
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
Alfa
AF:
0.00
Hom.:
0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
PhyloP100
2.1
Mutation Taster
=54/46
polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs530625473; hg19: chr7-96635363; API