1-178094500-T-A

Variant names:

• chr1-178094500-T-A
• rs1462912035
• NM_170692.4:c.8T>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_170692.4(RASAL2):​c.8T>A​(p.Leu3His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000143 in 1,402,884 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L3R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: RASAL2 NM_170692.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.05
• Publications: 0 publications found

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]

RASAL2-AS1 (HGNC:44170): (RASAL2 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13413566).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_170692.4. 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
	RASAL2	NM_170692.4	MANE Select	c.8T>A	p.Leu3His	missense	Exon 1 of 18	NP_733793.2	Q9UJF2-2
	RASAL2	NM_001437625.1		c.8T>A	p.Leu3His	missense	Exon 1 of 19	NP_001424554.1
	RASAL2	NM_001437626.1		c.8T>A	p.Leu3His	missense	Exon 1 of 18	NP_001424555.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RASAL2	ENST00000367649.8	TSL:1 MANE Select	c.8T>A	p.Leu3His	missense	Exon 1 of 18	ENSP00000356621.3	Q9UJF2-2
	RASAL2	ENST00000902905.1		c.8T>A	p.Leu3His	missense	Exon 1 of 18	ENSP00000572964.1
	RASAL2-AS1	ENST00000767999.1		n.-56A>T		upstream_gene	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000143 AC: 2 AN: 1402884 Hom.: 0 Cov.: 32 AF XY: 0.00000144 AC XY: 1 AN XY: 692902

African (AFR) AF: 0.00 AC: 0 AN: 31790

American (AMR) AF: 0.00 AC: 0 AN: 36422

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25206

East Asian (EAS) AF: 0.00 AC: 0 AN: 36080

South Asian (SAS) AF: 0.0000250 AC: 2 AN: 79856

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47566

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4692

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1083152

Other (OTH) AF: 0.00 AC: 0 AN: 58120

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.53
CADD	Uncertain	25
DANN	Uncertain	0.98
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.097
FATHMM_MKL	Benign	0.30	N
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.1	T
PhyloP100		1.0
PrimateAI	Pathogenic	0.80	D
PROVEAN	Benign	-0.53	N
REVEL	Benign	0.075
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Vest4		0.36
MutPred		0.19		Loss of sheet (P = 0.0228)
MVP		0.18
MPC		0.91
ClinPred		0.87	D
GERP RS		4.7
PromoterAI		-0.039	Neutral
gMVP		0.43
Mutation Taster		=292/8	polymorphism

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: rs1462912035; hg19: chr1-178063635;