1-178094575-C-T

Variant names:

• chr1-178094575-C-T
• NM_170692.4:c.83C>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.83C>T​(p.Pro28Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000689 in 1,452,248 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/18 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. P28Q) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: RASAL2 NM_170692.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.06

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=0.1835376).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RASAL2	NM_170692.4	c.83C>T	p.Pro28Leu	missense_variant	Exon 1 of 18	ENST00000367649.8	NP_733793.2
RASAL2	XM_011510166.3	c.83C>T	p.Pro28Leu	missense_variant	Exon 1 of 19		XP_011508468.1
RASAL2	XM_011510167.3	c.83C>T	p.Pro28Leu	missense_variant	Exon 1 of 18		XP_011508469.1
RASAL2	XM_047434837.1	c.83C>T	p.Pro28Leu	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.83C>T	p.Pro28Leu	missense_variant	Exon 1 of 18	1	NM_170692.4	ENSP00000356621.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.89e-7 AC: 1 AN: 1452248 Hom.: 0 Cov.: 32 AF XY: 0.00000139 AC XY: 1 AN XY: 721734

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: 9.03e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	23
DANN	Uncertain	1.0
Eigen	Benign	0.14
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Benign	0.43	N
LIST_S2	Benign	0.85	D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-1.1	T
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-0.83	N
REVEL	Benign	0.048
Sift	Uncertain	0.0080	D
Sift4G	Pathogenic	0.0	D
Vest4		0.23
MutPred		0.25		Loss of glycosylation at S25 (P = 0.0607);
MVP		0.27
MPC		0.28
ClinPred		0.98	D
GERP RS		4.7
gMVP		0.29

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-178063710;