rs765908750

Variant names:

• chr1-178299992-A-C
• rs765908750
• NM_170692.4:c.331A>C

Your query was ambiguous. Multiple possible variants found:

• chr1-178299992-A-C
• chr1-178299992-A-G
• chr1-178299992-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_170692.4(RASAL2):​c.331A>C​(p.Ile111Leu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RASAL2 NM_170692.4 missense, splice_region
• Scores: Splicing: ADA: 0.0003155
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.32

Genes affected

RASAL2 (HGNC:9874): (RAS protein activator like 2) This gene encodes a protein that contains the GAP-related domain (GRD), a characteristic domain of GTPase-activating proteins (GAPs). GAPs function as activators of Ras superfamily of small GTPases. The protein encoded by this gene is able to complement the defective RasGAP function in a yeast system. Two alternatively spliced transcript variants of this gene encoding distinct isoforms have been reported. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08251837).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RASAL2	NM_170692.4	c.331A>C	p.Ile111Leu	missense_variant, splice_region_variant	Exon 3 of 18	ENST00000367649.8	NP_733793.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RASAL2	ENST00000367649.8	c.331A>C	p.Ile111Leu	missense_variant, splice_region_variant	Exon 3 of 18	1	NM_170692.4	ENSP00000356621.3
RASAL2	ENST00000696605.1	c.718A>C	p.Ile240Leu	missense_variant, splice_region_variant	Exon 3 of 18			ENSP00000512749.1
RASAL2	ENST00000465723.1	n.655A>C		splice_region_variant, non_coding_transcript_exon_variant	Exon 6 of 6	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	16
DANN	Benign	0.66
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.85
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.0025	T
MetaRNN	Benign	0.083	T
MetaSVM	Benign	-1.0	T
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-0.030	N
REVEL	Benign	0.040
Sift	Benign	0.33	T
Sift4G	Benign	0.58	T
Vest4		0.24
MutPred		0.18		Loss of methylation at K109 (P = 0.0658);
MVP		0.088
MPC		0.22
ClinPred		0.23	T
GERP RS		-1.4
gMVP		0.097

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00032
dbscSNV1_RF	Benign	0.040
SpliceAI score (max)		0.090		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: rs765908750; hg19: chr1-178269127;