Genetic Variant GRAP2:c.*1141T>C (chr22-39972225-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_004810.4(GRAP2):c.*1141T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.819 in 152,440 control chromosomes in the GnomAD database, including 51,748 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 0.82 ( 51688 hom., cov: 35)

Exomes 𝑓: 0.89 ( 60 hom. )

Consequence

GRAP2
NM_004810.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.280

Publications

5 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:

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 (AFR) allele frequency at 95% confidence interval = 0.897 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004810.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GRAP2	NM_004810.4	MANE Select	c.*1141T>C	3_prime_UTR	Exon 8 of 8	NP_004801.1	O75791-1
GRAP2	NM_001291824.2		c.*1141T>C	3_prime_UTR	Exon 8 of 8	NP_001278753.1	Q6FI14
GRAP2	NM_001291825.1		c.*1141T>C	3_prime_UTR	Exon 7 of 7	NP_001278754.1	O75791-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRAP2	ENST00000344138.9	TSL:1 MANE Select	c.*1141T>C		3_prime_UTR	Exon 8 of 8	ENSP00000339186.4	O75791-1
	GRAP2	ENST00000861558.1		c.*1141T>C		3_prime_UTR	Exon 8 of 8	ENSP00000531617.1

Frequencies

GnomAD3 genomes

AF:

0.818

AC:

124523

AN:

152170

Hom.:

51631

Cov.:

show subpopulations

Gnomad AFR

AF:

0.905

Gnomad AMI

AF:

0.817

Gnomad AMR

AF:

0.668

Gnomad ASJ

AF:

0.825

Gnomad EAS

AF:

0.498

Gnomad SAS

AF:

0.751

Gnomad FIN

AF:

0.873

Gnomad MID

AF:

0.835

Gnomad NFE

AF:

0.820

Gnomad OTH

AF:

0.800

GnomAD4 exome

AF:

0.888

AC:

135

AN:

152

Hom.:

Cov.:

AF XY:

0.877

AC XY:

AN XY:

106

show subpopulations

African (AFR)

AF:

1.00

AC:

AN:

American (AMR)

AF:

0.500

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

AN:

East Asian (EAS)

AF:

1.00

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.893

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.878

AC:

AN:

Other (OTH)

AF:

0.929

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.818

AC:

124638

AN:

152288

Hom.:

51688

Cov.:

AF XY:

0.814

AC XY:

60636

AN XY:

74462

show subpopulations

African (AFR)

AF:

0.905

AC:

37626

AN:

41570

American (AMR)

AF:

0.667

AC:

10210

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.825

AC:

2864

AN:

3470

East Asian (EAS)

AF:

0.498

AC:

2579

AN:

5178

South Asian (SAS)

AF:

0.752

AC:

3632

AN:

4832

European-Finnish (FIN)

AF:

0.873

AC:

9262

AN:

10612

Middle Eastern (MID)

AF:

0.840

AC:

247

AN:

294

European-Non Finnish (NFE)

AF:

0.820

AC:

55779

AN:

68010

Other (OTH)

AF:

0.801

AC:

1694

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1157

2314

3471

4628

5785

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

876

1752

2628

3504

4380

<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:

0.811

Hom.:

81046

Bravo

AF:

0.803

Asia WGS

AF:

0.665

AC:

2317

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

2.1

(source)

DANN

Benign

0.51

PhyloP100

-0.28

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