rs138012

Positions:

• chr22-39972604-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.986

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
GRAP2	NM_004810.4	c.*1520G>A		3_prime_UTR_variant	8/8	ENST00000344138.9	NP_004801.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRAP2	ENST00000344138.9	c.*1520G>A		3_prime_UTR_variant	8/8	1	NM_004810.4	ENSP00000339186	P1

Frequencies

GnomAD3 genomes AF: 0.811 AC: 123369 AN: 152080 Hom.: 50694 Cov.: 32

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: 13 AN: 18 Hom.: 4 Cov.: 0 AF XY: 0.750 AC XY: 12 AN XY: 16

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.786

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.811 AC: 123481 AN: 152198 Hom.: 50748 Cov.: 32 AF XY: 0.806 AC XY: 59972 AN XY: 74420

Gnomad4 AFR AF: 0.896

Gnomad4 AMR AF: 0.663

Gnomad4 ASJ AF: 0.824

Gnomad4 EAS AF: 0.491

Gnomad4 SAS AF: 0.750

Gnomad4 FIN AF: 0.842

Gnomad4 NFE AF: 0.817

Gnomad4 OTH AF: 0.795

Alfa AF: 0.819 Hom.: 6353

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
DANN	Benign	0.62
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Other links and lift over

dbSNP: rs138012; hg19: chr22-40368608;