rs2281122

chr22-35547937-T-C

Variant summary

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

The NM_014310.4(RASD2):c.271+857T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.777 in 152,188 control chromosomes in the GnomAD database, including 46,225 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 0.78 (46225 hom., cov: 34)
• Consequence: RASD2 NM_014310.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.898

Genes affected

RASD2 (HGNC:18229): (RASD family member 2) This gene belongs to the Ras superfamily of small GTPases and is enriched in the striatum. The encoded protein functions as an E3 ligase for attachment of small ubiquitin-like modifier (SUMO). This protein also binds to mutant huntingtin (mHtt), the protein mutated in Huntington disease (HD). Sumoylation of mHTT by this protein may cause degeneration of the striatum. The protein functions as an activator of mechanistic target of rapamycin 1 (mTOR1), which in turn plays a role in myelination, axon growth and regeneration. Reduced levels of mRNA expressed by this gene were found in HD patients. [provided by RefSeq, Jan 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.843 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RASD2	NM_014310.4	c.271+857T>C		intron_variant		ENST00000216127.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RASD2	ENST00000216127.5	c.271+857T>C		intron_variant		1	NM_014310.4	P1

Frequencies

GnomAD3 genomes AF: 0.777 AC: 118229 AN: 152068 Hom.: 46216 Cov.: 34

Gnomad AFR AF: 0.700

Gnomad AMI AF: 0.865

Gnomad AMR AF: 0.751

Gnomad ASJ AF: 0.745

Gnomad EAS AF: 0.848

Gnomad SAS AF: 0.866

Gnomad FIN AF: 0.787

Gnomad MID AF: 0.851

Gnomad NFE AF: 0.818

Gnomad OTH AF: 0.778

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

GnomAD4 genome AF: 0.777 AC: 118284 AN: 152188 Hom.: 46225 Cov.: 34 AF XY: 0.778 AC XY: 57864 AN XY: 74390

Gnomad4 AFR AF: 0.699

Gnomad4 AMR AF: 0.751

Gnomad4 ASJ AF: 0.745

Gnomad4 EAS AF: 0.848

Gnomad4 SAS AF: 0.865

Gnomad4 FIN AF: 0.787

Gnomad4 NFE AF: 0.818

Gnomad4 OTH AF: 0.782

Alfa AF: 0.808 Hom.: 66355

Bravo AF: 0.767

Asia WGS AF: 0.836 AC: 2908 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	4.9
Dann	Benign	0.56

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: rs2281122; hg19: chr22-35943984;