1-178300011-A-T

Variant names:

• chr1-178300011-A-T
• rs201333128
• NM_170692.4:c.350A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_170692.4(RASAL2):​c.350A>T​(p.Gln117Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000795 in 1,613,822 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00035 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00084 (1 hom.)
• Consequence: RASAL2 NM_170692.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.25
• 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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.07887593).

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.350A>T	p.Gln117Leu	missense	Exon 3 of 18	NP_733793.2	Q9UJF2-2
	RASAL2	NM_001437625.1		c.350A>T	p.Gln117Leu	missense	Exon 3 of 19	NP_001424554.1
	RASAL2	NM_001437626.1		c.350A>T	p.Gln117Leu	missense	Exon 3 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.350A>T	p.Gln117Leu	missense	Exon 3 of 18	ENSP00000356621.3	Q9UJF2-2
	RASAL2	ENST00000696605.1		c.737A>T	p.Gln246Leu	missense	Exon 3 of 18	ENSP00000512749.1	A0A8Q3SIU1
	RASAL2	ENST00000902905.1		c.350A>T	p.Gln117Leu	missense	Exon 3 of 18	ENSP00000572964.1

Frequencies

GnomAD3 genomes AF: 0.000348 AC: 53 AN: 152226 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000314

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000393

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000500

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000303 AC: 76 AN: 251130 AF XY: 0.000273

Gnomad AFR exome AF: 0.000246

Gnomad AMR exome AF: 0.000232

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000555

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000842 AC: 1230 AN: 1461596 Hom.: 1 Cov.: 30 AF XY: 0.000811 AC XY: 590 AN XY: 727110

African (AFR) AF: 0.0000598 AC: 2 AN: 33466

American (AMR) AF: 0.000224 AC: 10 AN: 44658

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.00 AC: 0 AN: 86228

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53396

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 0.00106 AC: 1179 AN: 1111896

Other (OTH) AF: 0.000646 AC: 39 AN: 60384

GnomAD4 genome AF: 0.000348 AC: 53 AN: 152226 Hom.: 0 Cov.: 32 AF XY: 0.000202 AC XY: 15 AN XY: 74382

African (AFR) AF: 0.000314 AC: 13 AN: 41458

American (AMR) AF: 0.000393 AC: 6 AN: 15286

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000500 AC: 34 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.000663 Hom.: 0

Bravo AF: 0.000317

TwinsUK AF: 0.00135 AC: 5

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000581 AC: 5

ExAC AF: 0.000255 AC: 31

EpiCase AF: 0.000436

EpiControl AF: 0.000356

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	0.074
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	18
DANN	Uncertain	0.98
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.17
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.0054	T
MetaRNN	Benign	0.079	T
MetaSVM	Benign	-1.1	T
PhyloP100		2.3
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.022
Sift	Uncertain	0.011	D
Sift4G	Benign	0.18	T
Vest4		0.45
MVP		0.22
MPC		0.22
ClinPred		0.050	T
GERP RS		3.0
gMVP		0.29
Mutation Taster		=90/10	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: rs201333128; hg19: chr1-178269146;