Genetic Variant DLX6:p.Gln28_Gln43dup (chr7-97006052-G-GCAGCAGCAGCAGCAGCAGCAGCAACAGCAGCAGCAGCAGCAGCAGCAA) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

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

The NM_005222.4(DLX6):c.81_128dupGCAGCAGCAGCAGCAGCAACAGCAGCAGCAGCAGCAGCAGCAACAGCA(p.Gln28_Gln43dup) variant causes a disruptive inframe insertion change. 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. 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: 𝑓 0.00016 ( 0 hom., cov: 29)

Exomes 𝑓: 0.000014 ( 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: 4.05

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 links:

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]

DLX6-AS1 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_005222.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLX6	NM_005222.4	MANE Select	c.81_128dupGCAGCAGCAGCAGCAGCAACAGCAGCAGCAGCAGCAGCAGCAACAGCA	p.Gln28_Gln43dup	disruptive_inframe_insertion	Exon 1 of 3	NP_005213.3
	DLX6-AS1	NR_015448.1		n.141+7825_141+7872dupTTGCTGCTGCTGCTGCTGCTGCTGTTGCTGCTGCTGCTGCTGCTGCTG		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DLX6	ENST00000518156.3	TSL:1 MANE Select	c.81_128dupGCAGCAGCAGCAGCAGCAACAGCAGCAGCAGCAGCAGCAGCAACAGCA	p.Gln28_Gln43dup	disruptive_inframe_insertion	Exon 1 of 3	ENSP00000428480.2	P56179-3
DLX6-AS1	ENST00000458352.5	TSL:1	n.615+5725_615+5772dupTTGCTGCTGCTGCTGCTGCTGCTGTTGCTGCTGCTGCTGCTGCTGCTG		intron	N/A
DLX6-AS1	ENST00000430027.3	TSL:2	n.141+7825_141+7872dupTTGCTGCTGCTGCTGCTGCTGCTGTTGCTGCTGCTGCTGCTGCTGCTG		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.000161

AC:

AN:

149220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000990

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00106

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:

0.0000446

Gnomad OTH

AF:

0.000487

GnomAD2 exomes

AF:

0.00000585

AC:

AN:

170816

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000217

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000145

AC:

AN:

1382466

Hom.:

Cov.:

AF XY:

0.0000102

AC XY:

AN XY:

683666

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

31002

American (AMR)

AF:

0.000190

AC:

AN:

36896

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24598

East Asian (EAS)

AF:

0.0000570

AC:

AN:

35078

South Asian (SAS)

AF:

0.00

AC:

AN:

77586

European-Finnish (FIN)

AF:

0.00

AC:

AN:

44904

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5586

European-Non Finnish (NFE)

AF:

0.00000280

AC:

AN:

1069796

Other (OTH)

AF:

0.000140

AC:

AN:

57020

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0000000000426916), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.333

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000161

AC:

AN:

149322

Hom.:

Cov.:

AF XY:

0.000151

AC XY:

AN XY:

72942

show subpopulations

African (AFR)

AF:

0.0000988

AC:

AN:

40498

American (AMR)

AF:

0.00106

AC:

AN:

15052

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3446

East Asian (EAS)

AF:

0.00

AC:

AN:

4980

South Asian (SAS)

AF:

0.00

AC:

AN:

4746

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10064

Middle Eastern (MID)

AF:

0.00

AC:

AN:

284

European-Non Finnish (NFE)

AF:

0.0000446

AC:

AN:

67270

Other (OTH)

AF:

0.000483

AC:

AN:

2070

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

4.0

Mutation Taster

=40/60

disease causing

(source)

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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7-97006052-GCAGCAGCAGCAGCAGCAGCAGCAA-GCAGCAGCAGCAGCAGCAGCAGCAACAGCAGCAGCAGCAGCAGCAGCAACAGCAGCAGCAGCAGCAGCAGCAA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over