rs1242329205

Variant names:

• chr1-178094589-G-T
• rs1242329205
• NM_170692.4:c.97G>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.97G>T​(p.Asp33Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00000755 in 1,457,904 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000075 (0 hom.)
• Consequence: RASAL2 NM_170692.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.83

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=0.12540531).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RASAL2	NM_170692.4	c.97G>T	p.Asp33Tyr	missense_variant	Exon 1 of 18	ENST00000367649.8	NP_733793.2
RASAL2	XM_011510166.3	c.97G>T	p.Asp33Tyr	missense_variant	Exon 1 of 19		XP_011508468.1
RASAL2	XM_011510167.3	c.97G>T	p.Asp33Tyr	missense_variant	Exon 1 of 18		XP_011508469.1
RASAL2	XM_047434837.1	c.97G>T	p.Asp33Tyr	missense_variant	Exon 1 of 19		XP_047290793.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RASAL2	ENST00000367649.8	c.97G>T	p.Asp33Tyr	missense_variant	Exon 1 of 18	1	NM_170692.4	ENSP00000356621.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000755 AC: 11 AN: 1457904 Hom.: 0 Cov.: 32 AF XY: 0.00000828 AC XY: 6 AN XY: 724956

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000811

Gnomad4 OTH exome AF: 0.0000332

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 10, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.97G>T (p.D33Y) alteration is located in exon 1 (coding exon 1) of the RASAL2 gene. This alteration results from a G to T substitution at nucleotide position 97, causing the aspartic acid (D) at amino acid position 33 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Uncertain	25
DANN	Uncertain	0.98
Eigen	Benign	-0.15
Eigen_PC	Benign	0.039
FATHMM_MKL	Benign	0.42	N
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.0070	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.1	T
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-0.83	N
REVEL	Benign	0.028
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.0070	D
Vest4		0.15
MutPred		0.31		Loss of disorder (P = 0.0111);
MVP		0.19
MPC		0.30
ClinPred		0.89	D
GERP RS		4.7
gMVP		0.41

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

Publications

LitVar

Other links and lift over

dbSNP: rs1242329205; hg19: chr1-178063724;