dbSNP rs138012: GRAP2:c.*1520G>A (chr22-39972604-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_004810.4(GRAP2):c.*1520G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.811 in 152,216 control chromosomes in the GnomAD database, including 50,752 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 0.81 ( 50748 hom., cov: 32)

Exomes 𝑓: 0.72 ( 4 hom. )

Consequence

GRAP2
NM_004810.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.986

Publications

1 publications found

Variant links:

Genes affected

GRAP2 (HGNC:4563): (GRB2 related adaptor protein 2) This gene encodes a member of the GRB2/Sem5/Drk family. This member is an adaptor-like protein involved in leukocyte-specific protein-tyrosine kinase signaling. Like its related family member, GRB2-related adaptor protein (GRAP), this protein contains an SH2 domain flanked by two SH3 domains. This protein interacts with other proteins, such as GRB2-associated binding protein 1 (GAB1) and the SLP-76 leukocyte protein (LCP2), through its SH3 domains. Multiple alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Apr 2014]

GRAP2 links:

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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 (AFR) allele frequency at 95% confidence interval = 0.889 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRAP2	NM_004810.4 link	c.*1520G>A		3_prime_UTR_variant	Exon 8 of 8	ENST00000344138.9	NP_004801.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRAP2	ENST00000344138.9 link	c.*1520G>A		3_prime_UTR_variant	Exon 8 of 8	1	NM_004810.4	ENSP00000339186.4

Frequencies

GnomAD3 genomes

AF:

0.811

AC:

123369

AN:

152080

Hom.:

50694

Cov.:

show subpopulations

Gnomad AFR

AF:

0.896

Gnomad AMI

AF:

0.817

Gnomad AMR

AF:

0.663

Gnomad ASJ

AF:

0.824

Gnomad EAS

AF:

0.490

Gnomad SAS

AF:

0.750

Gnomad FIN

AF:

0.842

Gnomad MID

AF:

0.835

Gnomad NFE

AF:

0.817

Gnomad OTH

AF:

0.793

GnomAD4 exome

AF:

0.722

AC:

AN:

Hom.:

Cov.:

AF XY:

0.750

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.786

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.811

AC:

123481

AN:

152198

Hom.:

50748

Cov.:

AF XY:

0.806

AC XY:

59972

AN XY:

74420

show subpopulations

African (AFR)

AF:

0.896

AC:

37222

AN:

41534

American (AMR)

AF:

0.663

AC:

10141

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.824

AC:

2858

AN:

3470

East Asian (EAS)

AF:

0.491

AC:

2535

AN:

5168

South Asian (SAS)

AF:

0.750

AC:

3615

AN:

4818

European-Finnish (FIN)

AF:

0.842

AC:

8927

AN:

10608

Middle Eastern (MID)

AF:

0.840

AC:

247

AN:

294

European-Non Finnish (NFE)

AF:

0.817

AC:

55513

AN:

67980

Other (OTH)

AF:

0.795

AC:

1678

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1116

2233

3349

4466

5582

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

874

1748

2622

3496

4370

<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:

0.821

Hom.:

6665

Bravo

AF:

0.798

Asia WGS

AF:

0.660

AC:

2299

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

0.21

(source)

DANN

Benign

0.62

PhyloP100

-0.99

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over