Genetic Variant DLX1:c.*182C>G (chr2-172088439-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_178120.5(DLX1):c.*182C>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 0.0166 in 762,286 control chromosomes in the GnomAD database, including 238 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.015 ( 45 hom., cov: 33)

Exomes 𝑓: 0.017 ( 193 hom. )

Consequence

DLX1
NM_178120.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0640

Publications

3 publications found

Variant links:

Genes affected

DLX1 (HGNC:2914): (distal-less homeobox 1) This gene encodes a member of a homeobox transcription factor gene family similiar to the Drosophila distal-less gene. The encoded protein is localized to the nucleus where it may function as a transcriptional regulator of signals from multiple TGF-{beta} superfamily members. The encoded protein may play a role in the control of craniofacial patterning and the differentiation and survival of inhibitory neurons in the forebrain. This gene is located in a tail-to-tail configuration with another member of the family on the long arm of chromosome 2. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

DLX1 links:

ENSG00000288958 (HGNC:):

ENSG00000288958 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.065 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLX1	NM_178120.5 link	c.*182C>G		3_prime_UTR_variant	Exon 3 of 3	ENST00000361725.5	NP_835221.2	P56177-1X5D2F9
DLX1	NM_001038493.2 link	c.*360C>G		3_prime_UTR_variant	Exon 2 of 2		NP_001033582.1	P56177-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DLX1	ENST00000361725.5 link	c.*182C>G		3_prime_UTR_variant	Exon 3 of 3	1	NM_178120.5	ENSP00000354478.4		P56177-1

Frequencies

GnomAD3 genomes

AF:

0.0153

AC:

2324

AN:

152266

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00883

Gnomad ASJ

AF:

0.00518

Gnomad EAS

AF:

0.0608

Gnomad SAS

AF:

0.0711

Gnomad FIN

AF:

0.0462

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0136

Gnomad OTH

AF:

0.0105

GnomAD4 exome

AF:

0.0170

AC:

10351

AN:

609902

Hom.:

193

Cov.:

AF XY:

0.0176

AC XY:

5314

AN XY:

302258

show subpopulations

African (AFR)

AF:

0.00142

AC:

AN:

13412

American (AMR)

AF:

0.00893

AC:

AN:

8290

Ashkenazi Jewish (ASJ)

AF:

0.00309

AC:

AN:

12316

East Asian (EAS)

AF:

0.0648

AC:

1586

AN:

24470

South Asian (SAS)

AF:

0.0614

AC:

1419

AN:

23114

European-Finnish (FIN)

AF:

0.0439

AC:

1075

AN:

24482

Middle Eastern (MID)

AF:

0.0145

AC:

AN:

2074

European-Non Finnish (NFE)

AF:

0.0119

AC:

5616

AN:

472892

Other (OTH)

AF:

0.0171

AC:

494

AN:

28852

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

504

1008

1513

2017

2521

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0152

AC:

2323

AN:

152384

Hom.:

Cov.:

AF XY:

0.0177

AC XY:

1317

AN XY:

74516

show subpopulations

African (AFR)

AF:

0.00168

AC:

AN:

41594

American (AMR)

AF:

0.00882

AC:

135

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00518

AC:

AN:

3472

East Asian (EAS)

AF:

0.0608

AC:

315

AN:

5182

South Asian (SAS)

AF:

0.0712

AC:

344

AN:

4834

European-Finnish (FIN)

AF:

0.0462

AC:

491

AN:

10628

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0136

AC:

924

AN:

68044

Other (OTH)

AF:

0.0104

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

109

218

326

435

544

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00730

Hom.:

Bravo

AF:

0.0109

Asia WGS

AF:

0.0690

AC:

238

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

6.8

(source)

DANN

Benign

0.70

PhyloP100

0.064

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

2-172088439-C-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over