rs2281122

Variant names:

• chr22-35547937-T-C
• rs2281122
• NM_014310.4:c.271+857T>C

Variant summary

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

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
RASD2	NM_014310.4	c.271+857T>C		intron_variant	Intron 2 of 2	ENST00000216127.5	NP_055125.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RASD2	ENST00000216127.5	c.271+857T>C		intron_variant	Intron 2 of 2	1	NM_014310.4	ENSP00000216127.4

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

African (AFR) AF: 0.699 AC: 29028 AN: 41510

American (AMR) AF: 0.751 AC: 11485 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.745 AC: 2588 AN: 3472

East Asian (EAS) AF: 0.848 AC: 4377 AN: 5164

South Asian (SAS) AF: 0.865 AC: 4172 AN: 4824

European-Finnish (FIN) AF: 0.787 AC: 8329 AN: 10588

Middle Eastern (MID) AF: 0.847 AC: 249 AN: 294

European-Non Finnish (NFE) AF: 0.818 AC: 55618 AN: 68024

Other (OTH) AF: 0.782 AC: 1651 AN: 2112

Alfa AF: 0.804 Hom.: 82955

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
PhyloP100		-0.90
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2281122; hg19: chr22-35943984;