NM_020343.4:c.5543G>T

Variant names:

• chr20-20412101-C-A
• rs370762908
• NM_020343.4:c.5543G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020343.4(RALGAPA2):​c.5543G>T​(p.Arg1848Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,461,658 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. R1848C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: RALGAPA2 NM_020343.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.16
• Publications: 0 publications found

Genes affected

RALGAPA2 (HGNC:16207): (Ral GTPase activating protein catalytic subunit alpha 2) Predicted to enable GTPase activator activity and protein heterodimerization activity. Predicted to be involved in activation of GTPase activity. Predicted to act upstream of or within Ral protein signal transduction; regulation of exocyst localization; and regulation of protein localization. Located in cytosol and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13006616).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020343.4. 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
	RALGAPA2	NM_020343.4	MANE Select	c.5543G>T	p.Arg1848Leu	missense	Exon 38 of 40	NP_065076.2	Q2PPJ7-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RALGAPA2	ENST00000202677.12	TSL:5 MANE Select	c.5543G>T	p.Arg1848Leu	missense	Exon 38 of 40	ENSP00000202677.6	Q2PPJ7-1
	RALGAPA2	ENST00000909985.1		c.5504G>T	p.Arg1835Leu	missense	Exon 38 of 40	ENSP00000580044.1
	RALGAPA2	ENST00000934890.1		c.5405G>T	p.Arg1802Leu	missense	Exon 37 of 39	ENSP00000604949.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461658 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727116

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53398

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1111824

Other (OTH) AF: 0.00 AC: 0 AN: 60372

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	-0.040
CADD	Uncertain	23
DANN	Uncertain	0.98
Eigen	Benign	-0.13
Eigen_PC	Benign	0.11
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.27	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.13	T
MetaSVM	Uncertain	-0.15	T
PhyloP100		4.2
Vest4		0.22
MVP		0.49
ClinPred		0.74	D
GERP RS		5.9
Varity_R		0.13
Mutation Taster		=64/36	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs370762908; hg19: chr20-20392745;