Genetic Variant NM_005222.4:c.*9A>G (chr7-97010056-A-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_005222.4(DLX6):c.*9A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0147 in 1,581,382 control chromosomes in the GnomAD database, including 1,187 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.037 ( 268 hom., cov: 32)

Exomes 𝑓: 0.012 ( 919 hom. )

Consequence

DLX6
NM_005222.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.57

Publications

7 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: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.49).

BP6

Variant 7-97010056-A-G is Benign according to our data. Variant chr7-97010056-A-G is described in ClinVar as Benign. ClinVar VariationId is 1231769.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.133 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLX6	NM_005222.4 link	c.*9A>G		3_prime_UTR_variant	Exon 3 of 3	ENST00000518156.3	NP_005213.3
DLX6-AS1	NR_015448.1 link	n.141+3869T>C		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DLX6	ENST00000518156.3 link	c.*9A>G		3_prime_UTR_variant	Exon 3 of 3	1	NM_005222.4	ENSP00000428480.2

Frequencies

GnomAD3 genomes

AF:

0.0371

AC:

5648

AN:

152070

Hom.:

261

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0772

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0878

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.141

Gnomad SAS

AF:

0.0519

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000765

Gnomad OTH

AF:

0.0377

GnomAD2 exomes

AF:

0.0384

AC:

7521

AN:

195860

AF XY:

0.0354

show subpopulations

Gnomad AFR exome

AF:

0.0806

Gnomad AMR exome

AF:

0.115

Gnomad ASJ exome

AF:

0.000992

Gnomad EAS exome

AF:

0.147

Gnomad FIN exome

AF:

0.000159

Gnomad NFE exome

AF:

0.000438

Gnomad OTH exome

AF:

0.0233

GnomAD4 exome

AF:

0.0123

AC:

17627

AN:

1429194

Hom.:

919

Cov.:

AF XY:

0.0127

AC XY:

8964

AN XY:

707910

show subpopulations

African (AFR)

AF:

0.0761

AC:

2486

AN:

32672

American (AMR)

AF:

0.111

AC:

4330

AN:

38984

Ashkenazi Jewish (ASJ)

AF:

0.000942

AC:

AN:

25472

East Asian (EAS)

AF:

0.144

AC:

5438

AN:

37860

South Asian (SAS)

AF:

0.0460

AC:

3783

AN:

82182

European-Finnish (FIN)

AF:

0.000116

AC:

AN:

51524

Middle Eastern (MID)

AF:

0.00506

AC:

AN:

5736

European-Non Finnish (NFE)

AF:

0.000227

AC:

249

AN:

1095472

Other (OTH)

AF:

0.0216

AC:

1282

AN:

59292

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

936

1872

2807

3743

4679

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

270

540

810

1080

1350

<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:

0.0373

AC:

5683

AN:

152188

Hom.:

268

Cov.:

AF XY:

0.0397

AC XY:

2956

AN XY:

74422

show subpopulations

African (AFR)

AF:

0.0772

AC:

3208

AN:

41536

American (AMR)

AF:

0.0886

AC:

1355

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.000865

AC:

AN:

3470

East Asian (EAS)

AF:

0.141

AC:

726

AN:

5146

South Asian (SAS)

AF:

0.0517

AC:

249

AN:

4814

European-Finnish (FIN)

AF:

0.0000941

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000765

AC:

AN:

67978

Other (OTH)

AF:

0.0421

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

259

518

777

1036

1295

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

180

240

300

<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:

0.0241

Hom.:

276

Bravo

AF:

0.0451

Asia WGS

AF:

0.130

AC:

451

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

May 04, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Benign

0.82

PhyloP100

2.6

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over