22-35552218-G-C

Variant names:

• chr22-35552218-G-C
• rs736212
• NM_014310.4:c.*186G>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.*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
• Publications: 10 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.569 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014310.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RASD2	NM_014310.4	MANE Select	c.*186G>C		3_prime_UTR	Exon 3 of 3	NP_055125.2
	RASD2	NM_001366725.1		c.*186G>C		3_prime_UTR	Exon 3 of 3	NP_001353654.1	Q96D21
	RASD2	NM_001376515.1		c.*186G>C		3_prime_UTR	Exon 3 of 3	NP_001363444.1	Q96D21

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RASD2	ENST00000216127.5	TSL:1 MANE Select	c.*186G>C		3_prime_UTR	Exon 3 of 3	ENSP00000216127.4	Q96D21
	RASD2	ENST00000885869.1		c.*186G>C		3_prime_UTR	Exon 3 of 3	ENSP00000555928.1
	RASD2	ENST00000885870.1		c.*186G>C		3_prime_UTR	Exon 3 of 3	ENSP00000555929.1

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

African (AFR) AF: 0.430 AC: 6201 AN: 14424

American (AMR) AF: 0.441 AC: 8191 AN: 18568

Ashkenazi Jewish (ASJ) AF: 0.311 AC: 4460 AN: 14336

East Asian (EAS) AF: 0.566 AC: 17784 AN: 31402

South Asian (SAS) AF: 0.504 AC: 23400 AN: 46466

European-Finnish (FIN) AF: 0.219 AC: 6475 AN: 29540

Middle Eastern (MID) AF: 0.345 AC: 753 AN: 2182

European-Non Finnish (NFE) AF: 0.284 AC: 105148 AN: 370528

Other (OTH) AF: 0.340 AC: 10030 AN: 29510

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

African (AFR) AF: 0.434 AC: 17999 AN: 41462

American (AMR) AF: 0.407 AC: 6224 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.317 AC: 1099 AN: 3472

East Asian (EAS) AF: 0.586 AC: 3020 AN: 5152

South Asian (SAS) AF: 0.507 AC: 2442 AN: 4818

European-Finnish (FIN) AF: 0.206 AC: 2178 AN: 10590

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.280 AC: 19063 AN: 67962

Other (OTH) AF: 0.359 AC: 756 AN: 2108

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.51
DANN	Benign	0.52
PhyloP100		-1.8
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: rs736212; hg19: chr22-35948265;