rs2228184

chr2-172101522-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_004405.4(DLX2):c.525A>G(p.Gln175=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.398 in 1,613,662 control chromosomes in the GnomAD database, including 132,059 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 0.34 (10007 hom., cov: 34)
  • Exomes 𝑓: 0.40 (122052 hom.)
• Consequence: DLX2 NM_004405.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0400

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP7: Synonymous conserved (PhyloP=-0.04 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.609 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DLX2	NM_004405.4	c.525A>G	p.Gln175=	synonymous_variant	2/3	ENST00000234198.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DLX2	ENST00000234198.9	c.525A>G	p.Gln175=	synonymous_variant	2/3	1	NM_004405.4	P1
DLX2	ENST00000466293.2	c.525A>G	p.Gln175=	synonymous_variant	2/2	2

Frequencies

GnomAD3 genomes AF: 0.338 AC: 51375 AN: 152084 Hom.: 9991 Cov.: 34

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.411

Gnomad AMR AF: 0.327

Gnomad ASJ AF: 0.306

Gnomad EAS AF: 0.627

Gnomad SAS AF: 0.426

Gnomad FIN AF: 0.469

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.408

Gnomad OTH AF: 0.333

GnomAD3 exomes AF: 0.401 AC: 100301 AN: 249896 Hom.: 21207 AF XY: 0.410 AC XY: 55456 AN XY: 135354

Gnomad AFR exome AF: 0.143

Gnomad AMR exome AF: 0.340

Gnomad ASJ exome AF: 0.312

Gnomad EAS exome AF: 0.632

Gnomad SAS exome AF: 0.425

Gnomad FIN exome AF: 0.463

Gnomad NFE exome AF: 0.411

Gnomad OTH exome AF: 0.380

GnomAD4 exome AF: 0.404 AC: 590718 AN: 1461460 Hom.: 122052 Cov.: 62 AF XY: 0.406 AC XY: 295053 AN XY: 727050

Gnomad4 AFR exome AF: 0.139

Gnomad4 AMR exome AF: 0.334

Gnomad4 ASJ exome AF: 0.310

Gnomad4 EAS exome AF: 0.609

Gnomad4 SAS exome AF: 0.434

Gnomad4 FIN exome AF: 0.462

Gnomad4 NFE exome AF: 0.406

Gnomad4 OTH exome AF: 0.384

GnomAD4 genome AF: 0.338 AC: 51418 AN: 152202 Hom.: 10007 Cov.: 34 AF XY: 0.346 AC XY: 25733 AN XY: 74398

Gnomad4 AFR AF: 0.148

Gnomad4 AMR AF: 0.328

Gnomad4 ASJ AF: 0.306

Gnomad4 EAS AF: 0.627

Gnomad4 SAS AF: 0.426

Gnomad4 FIN AF: 0.469

Gnomad4 NFE AF: 0.408

Gnomad4 OTH AF: 0.332

Alfa AF: 0.382 Hom.: 15233

Bravo AF: 0.319

Asia WGS AF: 0.464 AC: 1617 AN: 3478

EpiCase AF: 0.395

EpiControl AF: 0.401

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
Cadd	Benign	4.0
Dann	Benign	0.58

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2228184; hg19: chr2-172966250; COSMIC: COSV52232936; COSMIC: COSV52232936;