20-20653462-T-C

Position:

• chr20-20653462-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020343.4(RALGAPA2):​c.328+68A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0518 in 857,064 control chromosomes in the GnomAD database, including 1,572 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.053 (288 hom., cov: 32)
  • Exomes 𝑓: 0.052 (1284 hom.)
• Consequence: RALGAPA2 NM_020343.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.26

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.153 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RALGAPA2	NM_020343.4	c.328+68A>G		intron_variant		ENST00000202677.12	NP_065076.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RALGAPA2	ENST00000202677.12	c.328+68A>G		intron_variant		5	NM_020343.4	ENSP00000202677	P1

Frequencies

GnomAD3 genomes AF: 0.0528 AC: 8033 AN: 152076 Hom.: 287 Cov.: 32

Gnomad AFR AF: 0.0525

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.0579

Gnomad ASJ AF: 0.0519

Gnomad EAS AF: 0.162

Gnomad SAS AF: 0.0807

Gnomad FIN AF: 0.0734

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0392

Gnomad OTH AF: 0.0451

GnomAD4 exome AF: 0.0516 AC: 36340 AN: 704870 Hom.: 1284 AF XY: 0.0522 AC XY: 19381 AN XY: 371380

Gnomad4 AFR exome AF: 0.0586

Gnomad4 AMR exome AF: 0.0685

Gnomad4 ASJ exome AF: 0.0643

Gnomad4 EAS exome AF: 0.133

Gnomad4 SAS exome AF: 0.0758

Gnomad4 FIN exome AF: 0.0699

Gnomad4 NFE exome AF: 0.0385

Gnomad4 OTH exome AF: 0.0573

GnomAD4 genome AF: 0.0529 AC: 8055 AN: 152194 Hom.: 288 Cov.: 32 AF XY: 0.0549 AC XY: 4085 AN XY: 74432

Gnomad4 AFR AF: 0.0527

Gnomad4 AMR AF: 0.0581

Gnomad4 ASJ AF: 0.0519

Gnomad4 EAS AF: 0.162

Gnomad4 SAS AF: 0.0801

Gnomad4 FIN AF: 0.0734

Gnomad4 NFE AF: 0.0392

Gnomad4 OTH AF: 0.0479

Alfa AF: 0.0436 Hom.: 24

Bravo AF: 0.0514

Asia WGS AF: 0.115 AC: 400 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.3
DANN	Benign	0.67

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: rs6132333; hg19: chr20-20634106; COSMIC: COSV52505239;