rs12261515

chr10-49386463-C-Achr10-49386463-C-Gchr10-49386463-C-T

Variant summary

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

The NM_001276451.2(DRGX):c.526+15G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.239 in 1,531,210 control chromosomes in the GnomAD database, including 45,641 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 0.25 (5014 hom., cov: 32)
  • Exomes 𝑓: 0.24 (40627 hom.)
• Consequence: DRGX NM_001276451.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.33

Genes affected

DRGX (HGNC:21536): (dorsal root ganglia homeobox) Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to act upstream of or within several processes, including detection of temperature stimulus; nervous system development; and sensory perception of mechanical stimulus. Predicted to be located in nucleus. Predicted to be part of chromatin. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.502 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DRGX	NM_001276451.2	c.526+15G>T		intron_variant		ENST00000374139.8
DRGX	XM_011540089.4	c.631+15G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DRGX	ENST00000374139.8	c.526+15G>T		intron_variant		2	NM_001276451.2	P1

Frequencies

GnomAD3 genomes AF: 0.249 AC: 37895 AN: 151892 Hom.: 5006 Cov.: 32

Gnomad AFR AF: 0.256

Gnomad AMI AF: 0.184

Gnomad AMR AF: 0.251

Gnomad ASJ AF: 0.196

Gnomad EAS AF: 0.518

Gnomad SAS AF: 0.231

Gnomad FIN AF: 0.284

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.224

Gnomad OTH AF: 0.246

GnomAD3 exomes AF: 0.267 AC: 39291 AN: 147378 Hom.: 5783 AF XY: 0.264 AC XY: 20545 AN XY: 77848

Gnomad AFR exome AF: 0.261

Gnomad AMR exome AF: 0.251

Gnomad ASJ exome AF: 0.192

Gnomad EAS exome AF: 0.543

Gnomad SAS exome AF: 0.236

Gnomad FIN exome AF: 0.289

Gnomad NFE exome AF: 0.234

Gnomad OTH exome AF: 0.259

GnomAD4 exome AF: 0.237 AC: 327554 AN: 1379200 Hom.: 40627 Cov.: 32 AF XY: 0.237 AC XY: 160590 AN XY: 678718

Gnomad4 AFR exome AF: 0.254

Gnomad4 AMR exome AF: 0.250

Gnomad4 ASJ exome AF: 0.184

Gnomad4 EAS exome AF: 0.487

Gnomad4 SAS exome AF: 0.232

Gnomad4 FIN exome AF: 0.283

Gnomad4 NFE exome AF: 0.228

Gnomad4 OTH exome AF: 0.238

GnomAD4 genome AF: 0.249 AC: 37925 AN: 152010 Hom.: 5014 Cov.: 32 AF XY: 0.252 AC XY: 18684 AN XY: 74278

Gnomad4 AFR AF: 0.255

Gnomad4 AMR AF: 0.251

Gnomad4 ASJ AF: 0.196

Gnomad4 EAS AF: 0.519

Gnomad4 SAS AF: 0.232

Gnomad4 FIN AF: 0.284

Gnomad4 NFE AF: 0.224

Gnomad4 OTH AF: 0.253

Alfa AF: 0.198 Hom.: 1332

Bravo AF: 0.251

Asia WGS AF: 0.349 AC: 1211 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	0.035
Dann	Benign	0.52

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs12261515; hg19: chr10-50594509; COSMIC: COSV65137098;