2-172102574-C-T

Position:

• chr2-172102574-C-T

Variant summary

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

The NM_004405.4(DLX2):​c.-36G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.449 in 1,472,780 control chromosomes in the GnomAD database, including 152,542 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 0.40 (12634 hom., cov: 32)
  • Exomes 𝑓: 0.46 (139908 hom.)
• Consequence: DLX2 NM_004405.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.731

Genes affected

DLX2 (HGNC:2915): (distal-less homeobox 2) Many vertebrate homeo box-containing genes have been identified on the basis of their sequence similarity with Drosophila developmental genes. Members of the Dlx gene family contain a homeobox that is related to that of Distal-less (Dll), a gene expressed in the head and limbs of the developing fruit fly. The Distal-less (Dlx) family of genes comprises at least 6 different members, DLX1-DLX6. The DLX proteins are postulated to play a role in forebrain and craniofacial development. This gene is located in a tail-to-tail configuration with another member of the gene family on the long arm of chromosome 2. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.466 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DLX2	NM_004405.4	c.-36G>A		5_prime_UTR_variant	1/3	ENST00000234198.9	NP_004396.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DLX2	ENST00000234198.9	c.-36G>A		5_prime_UTR_variant	1/3	1	NM_004405.4	ENSP00000234198	P1
DLX2	ENST00000466293.2	c.-36G>A		5_prime_UTR_variant	1/2	2		ENSP00000446904

Frequencies

GnomAD3 genomes AF: 0.396 AC: 60165 AN: 151888 Hom.: 12619 Cov.: 32

Gnomad AFR AF: 0.265

Gnomad AMI AF: 0.445

Gnomad AMR AF: 0.420

Gnomad ASJ AF: 0.470

Gnomad EAS AF: 0.200

Gnomad SAS AF: 0.341

Gnomad FIN AF: 0.494

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.470

Gnomad OTH AF: 0.414

GnomAD3 exomes AF: 0.418 AC: 36387 AN: 87148 Hom.: 8037 AF XY: 0.416 AC XY: 18191 AN XY: 43684

Gnomad AFR exome AF: 0.264

Gnomad AMR exome AF: 0.440

Gnomad ASJ exome AF: 0.499

Gnomad EAS exome AF: 0.198

Gnomad SAS exome AF: 0.370

Gnomad FIN exome AF: 0.496

Gnomad NFE exome AF: 0.477

Gnomad OTH exome AF: 0.422

GnomAD4 exome AF: 0.455 AC: 601204 AN: 1320776 Hom.: 139908 Cov.: 34 AF XY: 0.452 AC XY: 291537 AN XY: 644420

Gnomad4 AFR exome AF: 0.247

Gnomad4 AMR exome AF: 0.444

Gnomad4 ASJ exome AF: 0.480

Gnomad4 EAS exome AF: 0.196

Gnomad4 SAS exome AF: 0.362

Gnomad4 FIN exome AF: 0.494

Gnomad4 NFE exome AF: 0.475

Gnomad4 OTH exome AF: 0.431

GnomAD4 genome AF: 0.396 AC: 60211 AN: 152004 Hom.: 12634 Cov.: 32 AF XY: 0.393 AC XY: 29216 AN XY: 74288

Gnomad4 AFR AF: 0.265

Gnomad4 AMR AF: 0.421

Gnomad4 ASJ AF: 0.470

Gnomad4 EAS AF: 0.201

Gnomad4 SAS AF: 0.340

Gnomad4 FIN AF: 0.494

Gnomad4 NFE AF: 0.470

Gnomad4 OTH AF: 0.409

Alfa AF: 0.445 Hom.: 6769

Bravo AF: 0.385

Asia WGS AF: 0.270 AC: 943 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	14
DANN	Benign	0.84

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: rs743605; hg19: chr2-172967302; COSMIC: COSV52232224; COSMIC: COSV52232224;