NM_001276451.2:c.526+15G>T

Variant names:

• chr10-49386463-C-A
• rs12261515
• NM_001276451.2:c.526+15G>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001276451.2. 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
	DRGX	NM_001276451.2	MANE Select	c.526+15G>T		intron	N/A	NP_001263380.1	A6NNA5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DRGX	ENST00000374139.8	TSL:2 MANE Select	c.526+15G>T		intron	N/A	ENSP00000363254.1	A6NNA5
	DRGX	ENST00000891545.1		c.526+15G>T		intron	N/A	ENSP00000561604.1
	DRGX	ENST00000967011.1		c.526+15G>T		intron	N/A	ENSP00000637070.1

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

GnomAD2 exomes AF: 0.267 AC: 39291 AN: 147378 AF XY: 0.264

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 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

African (AFR) AF: 0.254 AC: 7847 AN: 30936

American (AMR) AF: 0.250 AC: 8055 AN: 32162

Ashkenazi Jewish (ASJ) AF: 0.184 AC: 4291 AN: 23372

East Asian (EAS) AF: 0.487 AC: 17576 AN: 36102

South Asian (SAS) AF: 0.232 AC: 17436 AN: 75268

European-Finnish (FIN) AF: 0.283 AC: 13892 AN: 49004

Middle Eastern (MID) AF: 0.248 AC: 1127 AN: 4548

European-Non Finnish (NFE) AF: 0.228 AC: 243752 AN: 1070782

Other (OTH) AF: 0.238 AC: 13578 AN: 57026

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

African (AFR) AF: 0.255 AC: 10578 AN: 41444

American (AMR) AF: 0.251 AC: 3836 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.196 AC: 680 AN: 3472

East Asian (EAS) AF: 0.519 AC: 2669 AN: 5146

South Asian (SAS) AF: 0.232 AC: 1117 AN: 4824

European-Finnish (FIN) AF: 0.284 AC: 3002 AN: 10572

Middle Eastern (MID) AF: 0.310 AC: 91 AN: 294

European-Non Finnish (NFE) AF: 0.224 AC: 15250 AN: 67962

Other (OTH) AF: 0.253 AC: 535 AN: 2112

Alfa AF: 0.202 Hom.: 1672

Bravo AF: 0.251

Asia WGS AF: 0.349 AC: 1211 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.035
DANN	Benign	0.52
PhyloP100		-2.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12261515; hg19: chr10-50594509; COSMIC: COSV65137098;