Variant 22-39947144-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001291826.2(GRAP2):c.-87G>A variant causes a 5 prime UTR premature start codon gain change. The variant allele was found at a frequency of 0.00000137 in 1,455,594 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

GRAP2
NM_001291826.2 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.17

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:

GRAP2 (HGNC:):

GRAP2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.29386312).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRAP2	NM_004810.4 linkuse as main transcript	c.38G>A	p.Gly13Asp	missense_variant	2/8	ENST00000344138.9	NP_004801.1	O75791-1Q6FI14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRAP2	ENST00000344138.9 linkuse as main transcript	c.38G>A	p.Gly13Asp	missense_variant	2/8	1	NM_004810.4	ENSP00000339186.4		O75791-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1455594

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

724716

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000181

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 17, 2024

The c.38G>A (p.G13D) alteration is located in exon 2 (coding exon 1) of the GRAP2 gene. This alteration results from a G to A substitution at nucleotide position 38, causing the glycine (G) at amino acid position 13 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.88

BayesDel_addAF

Uncertain

0.026

BayesDel_noAF

Benign

-0.20

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.21

T;.;T

Eigen

Uncertain

0.33

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Benign

0.55

LIST_S2

Uncertain

0.90

.;D;D

M_CAP

Benign

0.014

MetaRNN

Benign

0.29

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.42

N;.;N

PrimateAI

Uncertain

0.69

PROVEAN

Benign

-1.3

N;N;N

REVEL

Benign

0.13

Sift

Benign

0.048

D;T;D

Sift4G

Benign

0.15

T;T;T

Polyphen

0.93

P;.;P

Vest4

0.58

MutPred

0.40

Loss of glycosylation at S12 (P = 0.0387);Loss of glycosylation at S12 (P = 0.0387);Loss of glycosylation at S12 (P = 0.0387);

MVP

0.69

MPC

1.4

ClinPred

0.92

GERP RS

5.7

Varity_R

0.22

gMVP

0.39

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over