rs12220898

Positions:

• chr10-49368588-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.527-2207G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0982 in 152,280 control chromosomes in the GnomAD database, including 948 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 0.098 (948 hom., cov: 33)
• Consequence: DRGX NM_001276451.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.476

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.135 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DRGX	NM_001276451.2	c.527-2207G>A		intron_variant		ENST00000374139.8	NP_001263380.1
DRGX	XM_011540089.4	c.632-2207G>A		intron_variant			XP_011538391.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DRGX	ENST00000374139.8	c.527-2207G>A		intron_variant		2	NM_001276451.2	ENSP00000363254	P1

Frequencies

GnomAD3 genomes AF: 0.0983 AC: 14950 AN: 152162 Hom.: 949 Cov.: 33

Gnomad AFR AF: 0.0323

Gnomad AMI AF: 0.0581

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.0677

Gnomad EAS AF: 0.103

Gnomad SAS AF: 0.0698

Gnomad FIN AF: 0.174

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.122

Gnomad OTH AF: 0.0817

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

GnomAD4 genome AF: 0.0982 AC: 14950 AN: 152280 Hom.: 948 Cov.: 33 AF XY: 0.102 AC XY: 7604 AN XY: 74456

Gnomad4 AFR AF: 0.0322

Gnomad4 AMR AF: 0.140

Gnomad4 ASJ AF: 0.0677

Gnomad4 EAS AF: 0.103

Gnomad4 SAS AF: 0.0701

Gnomad4 FIN AF: 0.174

Gnomad4 NFE AF: 0.122

Gnomad4 OTH AF: 0.0809

Alfa AF: 0.112 Hom.: 981

Bravo AF: 0.0936

Asia WGS AF: 0.0860 AC: 299 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	7.0
DANN	Benign	0.47

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: rs12220898; hg19: chr10-50576633;