rs2228184

Variant names:

• chr2-172101522-T-C
• rs2228184
• NM_004405.4:c.525A>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_004405.4(DLX2):​c.525A>G​(p.Gln175Gln) 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
• Publications: 19 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004405.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLX2	NM_004405.4	MANE Select	c.525A>G	p.Gln175Gln	synonymous	Exon 2 of 3	NP_004396.1	Q53QU7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLX2	ENST00000234198.9	TSL:1 MANE Select	c.525A>G	p.Gln175Gln	synonymous	Exon 2 of 3	ENSP00000234198.4	Q07687-1
	DLX2	ENST00000466293.2	TSL:2	c.525A>G	p.Gln175Gln	synonymous	Exon 2 of 2	ENSP00000446904.1	Q07687-2

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

GnomAD2 exomes AF: 0.401 AC: 100301 AN: 249896 AF XY: 0.410

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 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

African (AFR) AF: 0.139 AC: 4638 AN: 33480

American (AMR) AF: 0.334 AC: 14906 AN: 44648

Ashkenazi Jewish (ASJ) AF: 0.310 AC: 8111 AN: 26132

East Asian (EAS) AF: 0.609 AC: 24174 AN: 39682

South Asian (SAS) AF: 0.434 AC: 37390 AN: 86242

European-Finnish (FIN) AF: 0.462 AC: 24643 AN: 53332

Middle Eastern (MID) AF: 0.301 AC: 1736 AN: 5764

European-Non Finnish (NFE) AF: 0.406 AC: 451912 AN: 1111812

Other (OTH) AF: 0.384 AC: 23208 AN: 60368

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

African (AFR) AF: 0.148 AC: 6171 AN: 41560

American (AMR) AF: 0.328 AC: 5016 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.306 AC: 1063 AN: 3472

East Asian (EAS) AF: 0.627 AC: 3236 AN: 5160

South Asian (SAS) AF: 0.426 AC: 2055 AN: 4820

European-Finnish (FIN) AF: 0.469 AC: 4971 AN: 10598

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.408 AC: 27747 AN: 67970

Other (OTH) AF: 0.332 AC: 702 AN: 2112

Alfa AF: 0.378 Hom.: 20452

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	4.0
DANN	Benign	0.58
PhyloP100		-0.040
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2228184; hg19: chr2-172966250; COSMIC: COSV52232936; COSMIC: COSV52232936;