Genetic Variant NM_005222.4:c.93_98delGCAGCA (chr7-97006051-GGCAGCA-G) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP3BS2

The NM_005222.4(DLX6):c.93_98delGCAGCA(p.Gln32_Gln33del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.000298 in 1,582,078 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. Q31Q) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00047 ( 1 hom., cov: 29)

Exomes 𝑓: 0.00028 ( 1 hom. )

Consequence

DLX6
NM_005222.4 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1B:1

Conservation

PhyloP100: 6.66

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

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_005222.4

BS2

High AC in GnomAd4 at 71 AD gene.

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.93_98delGCAGCA	p.Gln32_Gln33del	disruptive_inframe_deletion	Exon 1 of 3	NP_005213.3
	DLX6-AS1	NR_015448.1		n.141+7868_141+7873delTGCTGC		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DLX6	ENST00000518156.3	TSL:1 MANE Select	c.93_98delGCAGCA	p.Gln32_Gln33del	disruptive_inframe_deletion	Exon 1 of 3	ENSP00000428480.2	P56179-3
DLX6-AS1	ENST00000458352.5	TSL:1	n.615+5768_615+5773delTGCTGC		intron	N/A
DLX6-AS1	ENST00000430027.3	TSL:2	n.141+7868_141+7873delTGCTGC		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.000473

AC:

AN:

150048

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000195

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000133

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00966

Gnomad SAS

AF:

0.000210

Gnomad FIN

AF:

0.0000993

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000134

Gnomad OTH

AF:

0.000485

GnomAD2 exomes

AF:

0.000796

AC:

151

AN:

189612

AF XY:

0.000650

show subpopulations

Gnomad AFR exome

AF:

0.000384

Gnomad AMR exome

AF:

0.000315

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00902

Gnomad FIN exome

AF:

0.000117

Gnomad NFE exome

AF:

0.000123

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000279

AC:

400

AN:

1431934

Hom.:

AF XY:

0.000259

AC XY:

184

AN XY:

710086

show subpopulations

African (AFR)

AF:

0.000275

AC:

AN:

32740

American (AMR)

AF:

0.000292

AC:

AN:

41150

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25640

East Asian (EAS)

AF:

0.00568

AC:

217

AN:

38212

South Asian (SAS)

AF:

0.000159

AC:

AN:

81958

European-Finnish (FIN)

AF:

0.0000200

AC:

AN:

49974

Middle Eastern (MID)

AF:

0.000175

AC:

AN:

5722

European-Non Finnish (NFE)

AF:

0.000118

AC:

130

AN:

1097368

Other (OTH)

AF:

0.000287

AC:

AN:

59170

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.418

Heterozygous variant carriers

112

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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

AF:

0.000473

AC:

AN:

150144

Hom.:

Cov.:

AF XY:

0.000518

AC XY:

AN XY:

73326

show subpopulations

African (AFR)

AF:

0.000195

AC:

AN:

41066

American (AMR)

AF:

0.000132

AC:

AN:

15104

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3450

East Asian (EAS)

AF:

0.00969

AC:

AN:

5058

South Asian (SAS)

AF:

0.000210

AC:

AN:

4758

European-Finnish (FIN)

AF:

0.0000993

AC:

AN:

10066

Middle Eastern (MID)

AF:

0.00

AC:

AN:

284

European-Non Finnish (NFE)

AF:

0.000134

AC:

AN:

67372

Other (OTH)

AF:

0.000482

AC:

AN:

2074

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

DLX6-related disorder (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

6.7

Mutation Taster

=187/13

polymorphism

(source)

Splicing

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

Publications

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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