Genetic Variant RALGAPA2:c.328+68A>G (chr20-20653462-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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. Variant has been reported in ClinVar as (no stars).

Frequency

Genomes: 𝑓 0.053 ( 288 hom., cov: 32)

Exomes 𝑓: 0.052 ( 1284 hom. )

Consequence

RALGAPA2
NM_020343.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.26

Publications

6 publications found

Variant links:

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]

RALGAPA2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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.

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.328+68A>G		intron	N/A	NP_065076.2	Q2PPJ7-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RALGAPA2	ENST00000202677.12	TSL:5 MANE Select	c.328+68A>G	intron	N/A	ENSP00000202677.6	Q2PPJ7-1
RALGAPA2	ENST00000909985.1		c.328+68A>G	intron	N/A	ENSP00000580044.1
RALGAPA2	ENST00000934890.1		c.328+68A>G	intron	N/A	ENSP00000604949.1

Frequencies

GnomAD3 genomes

AF:

0.0528

AC:

8033

AN:

152076

Hom.:

287

Cov.:

show subpopulations

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

show subpopulations

African (AFR)

AF:

0.0586

AC:

992

AN:

16942

American (AMR)

AF:

0.0685

AC:

1869

AN:

27290

Ashkenazi Jewish (ASJ)

AF:

0.0643

AC:

1288

AN:

20026

East Asian (EAS)

AF:

0.133

AC:

4294

AN:

32312

South Asian (SAS)

AF:

0.0758

AC:

4581

AN:

60396

European-Finnish (FIN)

AF:

0.0699

AC:

3349

AN:

47878

Middle Eastern (MID)

AF:

0.0567

AC:

237

AN:

4182

European-Non Finnish (NFE)

AF:

0.0385

AC:

17731

AN:

460974

Other (OTH)

AF:

0.0573

AC:

1999

AN:

34870

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1624

3248

4871

6495

8119

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

454

908

1362

1816

2270

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0529

AC:

8055

AN:

152194

Hom.:

288

Cov.:

AF XY:

0.0549

AC XY:

4085

AN XY:

74432

show subpopulations

African (AFR)

AF:

0.0527

AC:

2188

AN:

41542

American (AMR)

AF:

0.0581

AC:

888

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0519

AC:

180

AN:

3470

East Asian (EAS)

AF:

0.162

AC:

841

AN:

5182

South Asian (SAS)

AF:

0.0801

AC:

387

AN:

4830

European-Finnish (FIN)

AF:

0.0734

AC:

775

AN:

10558

Middle Eastern (MID)

AF:

0.0340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0392

AC:

2669

AN:

68008

Other (OTH)

AF:

0.0479

AC:

101

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

380

759

1139

1518

1898

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

192

288

384

480

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0450

Hom.:

281

Bravo

AF:

0.0514

Asia WGS

AF:

0.115

AC:

400

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

1.3

(source)

DANN

Benign

0.67

PhyloP100

-1.3

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over