NM_020343.4:c.5319C>T

Variant names:

• chr20-20495165-G-A
• rs117776965
• NM_020343.4:c.5319C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_020343.4(RALGAPA2):​c.5319C>T​(p.Tyr1773Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00517 in 1,611,074 control chromosomes in the GnomAD database, including 39 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0042 (2 hom., cov: 33)
  • Exomes 𝑓: 0.0053 (37 hom.)
• Consequence: RALGAPA2 NM_020343.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.49
• Publications: 4 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: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.024).
• BP6: Variant 20-20495165-G-A is Benign according to our data. Variant chr20-20495165-G-A is described in ClinVar as Benign. ClinVar VariationId is 789355.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=2.49 with no splicing effect.
• BS1: Variant frequency is greater than expected in population amr. GnomAdExome4 allele frequency = 0.00526 (7680/1458790) while in subpopulation AMR AF = 0.0217 (968/44650). AF 95% confidence interval is 0.0205. There are 37 homozygotes in GnomAdExome4. There are 3748 alleles in the male GnomAdExome4 subpopulation. Median coverage is 30. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

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.5319C>T	p.Tyr1773Tyr	synonymous	Exon 36 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.5319C>T	p.Tyr1773Tyr	synonymous	Exon 36 of 40	ENSP00000202677.6	Q2PPJ7-1
	RALGAPA2	ENST00000909985.1		c.5280C>T	p.Tyr1760Tyr	synonymous	Exon 36 of 40	ENSP00000580044.1
	RALGAPA2	ENST00000934890.1		c.5181C>T	p.Tyr1727Tyr	synonymous	Exon 35 of 39	ENSP00000604949.1

Frequencies

GnomAD3 genomes AF: 0.00423 AC: 644 AN: 152166 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.00125

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00871

Gnomad ASJ AF: 0.00519

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00393

Gnomad FIN AF: 0.00500

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00535

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.00734 AC: 1828 AN: 248924 AF XY: 0.00622

Gnomad AFR exome AF: 0.00129

Gnomad AMR exome AF: 0.0235

Gnomad ASJ exome AF: 0.00477

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00817

Gnomad NFE exome AF: 0.00538

Gnomad OTH exome AF: 0.00696

GnomAD4 exome AF: 0.00526 AC: 7680 AN: 1458790 Hom.: 37 Cov.: 30 AF XY: 0.00516 AC XY: 3748 AN XY: 725708

African (AFR) AF: 0.000957 AC: 32 AN: 33448

American (AMR) AF: 0.0217 AC: 968 AN: 44650

Ashkenazi Jewish (ASJ) AF: 0.00457 AC: 119 AN: 26016

East Asian (EAS) AF: 0.00 AC: 0 AN: 39674

South Asian (SAS) AF: 0.00427 AC: 367 AN: 85962

European-Finnish (FIN) AF: 0.00705 AC: 376 AN: 53346

Middle Eastern (MID) AF: 0.00104 AC: 6 AN: 5746

European-Non Finnish (NFE) AF: 0.00504 AC: 5593 AN: 1109744

Other (OTH) AF: 0.00364 AC: 219 AN: 60204

GnomAD4 genome AF: 0.00423 AC: 644 AN: 152284 Hom.: 2 Cov.: 33 AF XY: 0.00438 AC XY: 326 AN XY: 74462

African (AFR) AF: 0.00125 AC: 52 AN: 41564

American (AMR) AF: 0.00870 AC: 133 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00519 AC: 18 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00394 AC: 19 AN: 4826

European-Finnish (FIN) AF: 0.00500 AC: 53 AN: 10600

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

European-Non Finnish (NFE) AF: 0.00535 AC: 364 AN: 68022

Other (OTH) AF: 0.00237 AC: 5 AN: 2110

Alfa AF: 0.00480 Hom.: 1

Bravo AF: 0.00478

Asia WGS AF: 0.00346 AC: 12 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	7.4
DANN	Benign	0.53
PhyloP100		2.5
Mutation Taster		=100/0	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: rs117776965; hg19: chr20-20475809;