rs6518956

chr22-35545973-G-A

Variant summary

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

The NM_014310.4(RASD2):c.-9-828G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.54 in 151,950 control chromosomes in the GnomAD database, including 22,751 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 0.54 (22751 hom., cov: 31)
• Consequence: RASD2 NM_014310.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.783

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=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.583 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RASD2	NM_014310.4	c.-9-828G>A		intron_variant		ENST00000216127.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RASD2	ENST00000216127.5	c.-9-828G>A		intron_variant		1	NM_014310.4	P1

Frequencies

GnomAD3 genomes AF: 0.540 AC: 81983 AN: 151832 Hom.: 22748 Cov.: 31

Gnomad AFR AF: 0.543

Gnomad AMI AF: 0.646

Gnomad AMR AF: 0.425

Gnomad ASJ AF: 0.483

Gnomad EAS AF: 0.200

Gnomad SAS AF: 0.528

Gnomad FIN AF: 0.567

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.588

Gnomad OTH AF: 0.518

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

GnomAD4 genome AF: 0.540 AC: 82020 AN: 151950 Hom.: 22751 Cov.: 31 AF XY: 0.536 AC XY: 39798 AN XY: 74256

Gnomad4 AFR AF: 0.543

Gnomad4 AMR AF: 0.424

Gnomad4 ASJ AF: 0.483

Gnomad4 EAS AF: 0.200

Gnomad4 SAS AF: 0.527

Gnomad4 FIN AF: 0.567

Gnomad4 NFE AF: 0.588

Gnomad4 OTH AF: 0.512

Alfa AF: 0.568 Hom.: 32836

Bravo AF: 0.524

Asia WGS AF: 0.364 AC: 1266 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	7.9
Dann	Benign	0.78

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: rs6518956; hg19: chr22-35942020;