2-172102574-C-T

Variant names:

• chr2-172102574-C-T
• rs743605
• NM_004405.4:c.-36G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 17 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 -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.

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.-36G>A		5_prime_UTR	Exon 1 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.-36G>A		5_prime_UTR	Exon 1 of 3	ENSP00000234198.4	Q07687-1
	DLX2	ENST00000466293.2	TSL:2	c.-36G>A		5_prime_UTR	Exon 1 of 2	ENSP00000446904.1	Q07687-2

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

GnomAD2 exomes AF: 0.418 AC: 36387 AN: 87148 AF XY: 0.416

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 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

African (AFR) AF: 0.247 AC: 6986 AN: 28290

American (AMR) AF: 0.444 AC: 10024 AN: 22560

Ashkenazi Jewish (ASJ) AF: 0.480 AC: 9622 AN: 20050

East Asian (EAS) AF: 0.196 AC: 6786 AN: 34706

South Asian (SAS) AF: 0.362 AC: 24097 AN: 66622

European-Finnish (FIN) AF: 0.494 AC: 22714 AN: 46006

Middle Eastern (MID) AF: 0.328 AC: 1218 AN: 3718

European-Non Finnish (NFE) AF: 0.475 AC: 496310 AN: 1044462

Other (OTH) AF: 0.431 AC: 23447 AN: 54362

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

African (AFR) AF: 0.265 AC: 10986 AN: 41480

American (AMR) AF: 0.421 AC: 6423 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.470 AC: 1629 AN: 3468

East Asian (EAS) AF: 0.201 AC: 1034 AN: 5154

South Asian (SAS) AF: 0.340 AC: 1640 AN: 4818

European-Finnish (FIN) AF: 0.494 AC: 5226 AN: 10588

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.470 AC: 31914 AN: 67906

Other (OTH) AF: 0.409 AC: 864 AN: 2114

Alfa AF: 0.444 Hom.: 7900

Bravo AF: 0.385

Asia WGS AF: 0.270 AC: 943 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	14
DANN	Benign	0.84
PhyloP100		0.73
PromoterAI		-0.033	Neutral
Mutation Taster		=299/1	polymorphism (auto)

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

Other links and lift over

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