chr22-35552218-G-C

Position:

• chr22-35552218-G-C

Variant summary

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

The NM_014310.4(RASD2):​c.*186G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.332 in 709,008 control chromosomes in the GnomAD database, including 42,872 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 0.35 (10003 hom., cov: 32)
  • Exomes 𝑓: 0.33 (32869 hom.)
• Consequence: RASD2 NM_014310.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.75

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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.569 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RASD2	NM_014310.4	c.*186G>C		3_prime_UTR_variant	3/3	ENST00000216127.5	NP_055125.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RASD2	ENST00000216127.5	c.*186G>C		3_prime_UTR_variant	3/3	1	NM_014310.4	ENSP00000216127.4

Frequencies

GnomAD3 genomes AF: 0.350 AC: 53117 AN: 151934 Hom.: 9995 Cov.: 32

Gnomad AFR AF: 0.434

Gnomad AMI AF: 0.300

Gnomad AMR AF: 0.407

Gnomad ASJ AF: 0.317

Gnomad EAS AF: 0.587

Gnomad SAS AF: 0.508

Gnomad FIN AF: 0.206

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.280

Gnomad OTH AF: 0.351

GnomAD4 exome AF: 0.328 AC: 182442 AN: 556956 Hom.: 32869 Cov.: 7 AF XY: 0.335 AC XY: 95970 AN XY: 286538

Gnomad4 AFR exome AF: 0.430

Gnomad4 AMR exome AF: 0.441

Gnomad4 ASJ exome AF: 0.311

Gnomad4 EAS exome AF: 0.566

Gnomad4 SAS exome AF: 0.504

Gnomad4 FIN exome AF: 0.219

Gnomad4 NFE exome AF: 0.284

Gnomad4 OTH exome AF: 0.340

GnomAD4 genome AF: 0.350 AC: 53163 AN: 152052 Hom.: 10003 Cov.: 32 AF XY: 0.350 AC XY: 26043 AN XY: 74310

Gnomad4 AFR AF: 0.434

Gnomad4 AMR AF: 0.407

Gnomad4 ASJ AF: 0.317

Gnomad4 EAS AF: 0.586

Gnomad4 SAS AF: 0.507

Gnomad4 FIN AF: 0.206

Gnomad4 NFE AF: 0.280

Gnomad4 OTH AF: 0.359

Alfa AF: 0.185 Hom.: 373

Bravo AF: 0.367

Asia WGS AF: 0.541 AC: 1880 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.51
DANN	Benign	0.52

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: rs736212; hg19: chr22-35948265;