chr1-178094677-G-C

Variant names:

• chr1-178094677-G-C
• rs144829800
• NM_170692.4:c.185G>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_170692.4(RASAL2):​c.185G>C​(p.Ser62Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000279 in 1,614,114 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S62I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00039 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00027 (1 hom.)
• Consequence: RASAL2 NM_170692.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.62
• Publications: 2 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.04786232).

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.185G>C	p.Ser62Thr	missense	Exon 1 of 18	NP_733793.2	Q9UJF2-2
	RASAL2	NM_001437625.1		c.185G>C	p.Ser62Thr	missense	Exon 1 of 19	NP_001424554.1
	RASAL2	NM_001437626.1		c.185G>C	p.Ser62Thr	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.185G>C	p.Ser62Thr	missense	Exon 1 of 18	ENSP00000356621.3	Q9UJF2-2
	RASAL2	ENST00000902905.1		c.185G>C	p.Ser62Thr	missense	Exon 1 of 18	ENSP00000572964.1
	RASAL2-AS1	ENST00000767999.1		n.-233C>G		upstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.000387 AC: 59 AN: 152274 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000981

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000338

Gnomad OTH AF: 0.00574

GnomAD2 exomes AF: 0.000276 AC: 69 AN: 249874 AF XY: 0.000318

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000781

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000927

Gnomad NFE exome AF: 0.000293

Gnomad OTH exome AF: 0.00115

GnomAD4 exome AF: 0.000268 AC: 392 AN: 1461722 Hom.: 1 Cov.: 32 AF XY: 0.000267 AC XY: 194 AN XY: 727164

African (AFR) AF: 0.000299 AC: 10 AN: 33480

American (AMR) AF: 0.000827 AC: 37 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86246

European-Finnish (FIN) AF: 0.0000563 AC: 3 AN: 53276

Middle Eastern (MID) AF: 0.00347 AC: 20 AN: 5766

European-Non Finnish (NFE) AF: 0.000258 AC: 287 AN: 1112006

Other (OTH) AF: 0.000546 AC: 33 AN: 60396

GnomAD4 genome AF: 0.000387 AC: 59 AN: 152392 Hom.: 0 Cov.: 33 AF XY: 0.000443 AC XY: 33 AN XY: 74528

African (AFR) AF: 0.000168 AC: 7 AN: 41596

American (AMR) AF: 0.000980 AC: 15 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10632

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000338 AC: 23 AN: 68038

Other (OTH) AF: 0.00568 AC: 12 AN: 2114

Alfa AF: 0.000236 Hom.: 0

Bravo AF: 0.000370

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ExAC AF: 0.000264 AC: 32

EpiCase AF: 0.000709

EpiControl AF: 0.000533

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.54
CADD	Uncertain	24
DANN	Uncertain	0.98
Eigen	Benign	-0.092
Eigen_PC	Benign	0.060
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.0023	T
MetaRNN	Benign	0.048	T
MetaSVM	Benign	-1.1	T
PhyloP100		3.6
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-0.72	N
REVEL	Benign	0.035
Sift	Uncertain	0.029	D
Sift4G	Benign	0.12	T
Vest4		0.17
MVP		0.15
MPC		0.21
ClinPred		0.044	T
GERP RS		3.9
gMVP		0.43
Mutation Taster		=96/4	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: rs144829800; hg19: chr1-178063812;