10-49388668-C-A

Position:

• chr10-49388668-C-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BS1 BS2

The NM_001276451.2(DRGX):​c.234+1465G>T variant causes a intron change. The variant allele was found at a frequency of 0.0406 in 152,330 control chromosomes in the GnomAD database, including 170 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 0.041 (170 hom., cov: 33)
• Consequence: DRGX NM_001276451.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.75

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.28).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0406 (6192/152330) while in subpopulation AFR AF= 0.0513 (2131/41576). AF 95% confidence interval is 0.0494. There are 170 homozygotes in gnomad4. There are 3227 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 170 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DRGX	NM_001276451.2	c.234+1465G>T		intron_variant		ENST00000374139.8	NP_001263380.1
DRGX	XM_011540089.4	c.339+293G>T		intron_variant			XP_011538391.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DRGX	ENST00000374139.8	c.234+1465G>T		intron_variant		2	NM_001276451.2	ENSP00000363254	P1

Frequencies

GnomAD3 genomes AF: 0.0406 AC: 6182 AN: 152212 Hom.: 169 Cov.: 33

Gnomad AFR AF: 0.0513

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.0229

Gnomad ASJ AF: 0.0118

Gnomad EAS AF: 0.000384

Gnomad SAS AF: 0.0228

Gnomad FIN AF: 0.114

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0332

Gnomad OTH AF: 0.0335

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0406 AC: 6192 AN: 152330 Hom.: 170 Cov.: 33 AF XY: 0.0433 AC XY: 3227 AN XY: 74488

Gnomad4 AFR AF: 0.0513

Gnomad4 AMR AF: 0.0229

Gnomad4 ASJ AF: 0.0118

Gnomad4 EAS AF: 0.000385

Gnomad4 SAS AF: 0.0236

Gnomad4 FIN AF: 0.114

Gnomad4 NFE AF: 0.0332

Gnomad4 OTH AF: 0.0331

Alfa AF: 0.0365 Hom.: 25

Bravo AF: 0.0350

Asia WGS AF: 0.0140 AC: 49 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.28
CADD	Benign	21
DANN	Benign	0.86

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

Publications

LitVar

Other links and lift over

dbSNP: rs17010003; hg19: chr10-50596714;