rs3821186

Positions:

• chr2-172088439-C-G
• chr2-172088439-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0640

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
DLX1	NM_178120.5	c.*182C>G		3_prime_UTR_variant	3/3	ENST00000361725.5	NP_835221.2
DLX1	NM_001038493.2	c.*360C>G		3_prime_UTR_variant	2/2		NP_001033582.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DLX1	ENST00000361725.5	c.*182C>G		3_prime_UTR_variant	3/3	1	NM_178120.5	ENSP00000354478	P1
DLX1	ENST00000341900.6	c.*360C>G		3_prime_UTR_variant	2/2	1		ENSP00000341786
DLX1	ENST00000475989.2	n.1024C>G		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes AF: 0.0153 AC: 2324 AN: 152266 Hom.: 46 Cov.: 33

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.: 8 AF XY: 0.0176 AC XY: 5314 AN XY: 302258

Gnomad4 AFR exome AF: 0.00142

Gnomad4 AMR exome AF: 0.00893

Gnomad4 ASJ exome AF: 0.00309

Gnomad4 EAS exome AF: 0.0648

Gnomad4 SAS exome AF: 0.0614

Gnomad4 FIN exome AF: 0.0439

Gnomad4 NFE exome AF: 0.0119

Gnomad4 OTH exome AF: 0.0171

GnomAD4 genome AF: 0.0152 AC: 2323 AN: 152384 Hom.: 45 Cov.: 33 AF XY: 0.0177 AC XY: 1317 AN XY: 74516

Gnomad4 AFR AF: 0.00168

Gnomad4 AMR AF: 0.00882

Gnomad4 ASJ AF: 0.00518

Gnomad4 EAS AF: 0.0608

Gnomad4 SAS AF: 0.0712

Gnomad4 FIN AF: 0.0462

Gnomad4 NFE AF: 0.0136

Gnomad4 OTH AF: 0.0104

Alfa AF: 0.00730 Hom.: 1

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
DANN	Benign	0.70

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

LitVar

Other links and lift over

dbSNP: rs3821186; hg19: chr2-172953167;