chr1-178300103-G-A

Variant names:

• chr1-178300103-G-A
• rs141488130
• NM_170692.4:c.442G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_170692.4(RASAL2):​c.442G>A​(p.Gly148Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000145 in 1,613,052 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00014 (2 hom.)
• Consequence: RASAL2 NM_170692.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.09
• Publications: 4 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 -4 ACMG points.

• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

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.442G>A	p.Gly148Ser	missense	Exon 3 of 18	NP_733793.2	Q9UJF2-2
	RASAL2	NM_001437625.1		c.442G>A	p.Gly148Ser	missense	Exon 3 of 19	NP_001424554.1
	RASAL2	NM_001437626.1		c.442G>A	p.Gly148Ser	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.442G>A	p.Gly148Ser	missense	Exon 3 of 18	ENSP00000356621.3	Q9UJF2-2
	RASAL2	ENST00000696605.1		c.829G>A	p.Gly277Ser	missense	Exon 3 of 18	ENSP00000512749.1	A0A8Q3SIU1
	RASAL2	ENST00000902905.1		c.442G>A	p.Gly148Ser	missense	Exon 3 of 18	ENSP00000572964.1

Frequencies

GnomAD3 genomes AF: 0.000204 AC: 31 AN: 152136 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000397

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000112 AC: 28 AN: 249748 AF XY: 0.000163

Gnomad AFR exome AF: 0.0000616

Gnomad AMR exome AF: 0.0000879

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000186

Gnomad OTH exome AF: 0.000329

GnomAD4 exome AF: 0.000139 AC: 203 AN: 1460798 Hom.: 2 Cov.: 30 AF XY: 0.000155 AC XY: 113 AN XY: 726694

African (AFR) AF: 0.00 AC: 0 AN: 33434

American (AMR) AF: 0.0000899 AC: 4 AN: 44496

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26070

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.0000813 AC: 7 AN: 86060

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53384

Middle Eastern (MID) AF: 0.000525 AC: 3 AN: 5714

European-Non Finnish (NFE) AF: 0.000162 AC: 180 AN: 1111628

Other (OTH) AF: 0.000133 AC: 8 AN: 60322

GnomAD4 genome AF: 0.000204 AC: 31 AN: 152254 Hom.: 0 Cov.: 32 AF XY: 0.000107 AC XY: 8 AN XY: 74440

African (AFR) AF: 0.0000722 AC: 3 AN: 41550

American (AMR) AF: 0.00 AC: 0 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000397 AC: 27 AN: 68020

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.000210 Hom.: 0

Bravo AF: 0.000147

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000218

EpiControl AF: 0.000296

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	0.10
PhyloP100		7.1
gMVP		0.36
Mutation Taster		=85/15	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs141488130; hg19: chr1-178269238;