Genetic Variant NM_004810.4: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

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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