NM_020343.4:c.5426G>A

Variant names:

• chr20-20472898-C-T
• rs201178329
• NM_020343.4:c.5426G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_020343.4(RALGAPA2):​c.5426G>A​(p.Ser1809Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00116 in 1,613,614 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00091 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0012 (1 hom.)
• Consequence: RALGAPA2 NM_020343.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.17
• Publications: 5 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.05188471).

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.5426G>A	p.Ser1809Asn	missense	Exon 37 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.5426G>A	p.Ser1809Asn	missense	Exon 37 of 40	ENSP00000202677.6	Q2PPJ7-1
	RALGAPA2	ENST00000909985.1		c.5387G>A	p.Ser1796Asn	missense	Exon 37 of 40	ENSP00000580044.1
	RALGAPA2	ENST00000934890.1		c.5288G>A	p.Ser1763Asn	missense	Exon 36 of 39	ENSP00000604949.1

Frequencies

GnomAD3 genomes AF: 0.000907 AC: 138 AN: 152222 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000410

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00111

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.000282

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00143

Gnomad OTH AF: 0.000957

GnomAD2 exomes AF: 0.000720 AC: 179 AN: 248692 AF XY: 0.000786

Gnomad AFR exome AF: 0.000129

Gnomad AMR exome AF: 0.000436

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00123

Gnomad OTH exome AF: 0.000331

GnomAD4 exome AF: 0.00119 AC: 1740 AN: 1461274 Hom.: 1 Cov.: 30 AF XY: 0.00113 AC XY: 825 AN XY: 726920

African (AFR) AF: 0.000209 AC: 7 AN: 33442

American (AMR) AF: 0.000381 AC: 17 AN: 44644

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26118

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.000673 AC: 58 AN: 86238

European-Finnish (FIN) AF: 0.000225 AC: 12 AN: 53398

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5762

European-Non Finnish (NFE) AF: 0.00143 AC: 1586 AN: 1111628

Other (OTH) AF: 0.000944 AC: 57 AN: 60358

GnomAD4 genome AF: 0.000906 AC: 138 AN: 152340 Hom.: 0 Cov.: 32 AF XY: 0.000846 AC XY: 63 AN XY: 74496

African (AFR) AF: 0.000409 AC: 17 AN: 41572

American (AMR) AF: 0.00111 AC: 17 AN: 15302

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4832

European-Finnish (FIN) AF: 0.000282 AC: 3 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00143 AC: 97 AN: 68028

Other (OTH) AF: 0.000947 AC: 2 AN: 2112

Alfa AF: 0.00125 Hom.: 0

Bravo AF: 0.00114

TwinsUK AF: 0.00108 AC: 4

ALSPAC AF: 0.00156 AC: 6

ESP6500AA AF: 0.000251 AC: 1

ESP6500EA AF: 0.00155 AC: 13

ExAC AF: 0.000719 AC: 87

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000982

EpiControl AF: 0.00154

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	0.18
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.12
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.25	T
Eigen	Benign	-0.051
Eigen_PC	Benign	0.16
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.050	D
MetaRNN	Benign	0.052	T
MetaSVM	Uncertain	-0.013	T
MutationAssessor	Benign	0.71	N
PhyloP100		3.2
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-1.1	N
REVEL	Uncertain	0.34
Sift	Benign	0.20	T
Sift4G	Benign	0.50	T
Polyphen		0.0040	B
Vest4		0.69
MVP		0.66
MPC		0.092
ClinPred		0.042	T
GERP RS		5.6
Varity_R		0.12
gMVP		0.56
Mutation Taster		=83/17	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: rs201178329; hg19: chr20-20453542;