chr22-39911890-C-T

Position:

• chr22-39911890-C-T

Variant summary

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

The ENST00000344138.9(GRAP2):​c.-15+10560C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.455 in 151,930 control chromosomes in the GnomAD database, including 16,793 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 0.46 (16793 hom., cov: 31)
• Consequence: GRAP2 ENST00000344138.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.115

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 (HGNC:):

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 (EAS) allele frequency at 95% confidence interval = 0.653 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRAP2	NM_004810.4	c.-15+10560C>T		intron_variant		ENST00000344138.9	NP_004801.1
GRAP2	XM_047441607.1	c.-15+18000C>T		intron_variant			XP_047297563.1
GRAP2	XM_047441608.1	c.92+10560C>T		intron_variant			XP_047297564.1
GRAP2	XR_007067995.1	n.247+10560C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRAP2	ENST00000344138.9	c.-15+10560C>T		intron_variant		1	NM_004810.4	ENSP00000339186.4

Frequencies

GnomAD3 genomes AF: 0.455 AC: 69069 AN: 151812 Hom.: 16783 Cov.: 31

Gnomad AFR AF: 0.614

Gnomad AMI AF: 0.473

Gnomad AMR AF: 0.431

Gnomad ASJ AF: 0.361

Gnomad EAS AF: 0.672

Gnomad SAS AF: 0.479

Gnomad FIN AF: 0.326

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.371

Gnomad OTH AF: 0.433

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.455 AC: 69133 AN: 151930 Hom.: 16793 Cov.: 31 AF XY: 0.454 AC XY: 33707 AN XY: 74234

Gnomad4 AFR AF: 0.614

Gnomad4 AMR AF: 0.431

Gnomad4 ASJ AF: 0.361

Gnomad4 EAS AF: 0.672

Gnomad4 SAS AF: 0.479

Gnomad4 FIN AF: 0.326

Gnomad4 NFE AF: 0.371

Gnomad4 OTH AF: 0.435

Alfa AF: 0.397 Hom.: 1555

Bravo AF: 0.467

Asia WGS AF: 0.546 AC: 1899 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	1.6
DANN	Benign	0.74

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: rs137967; hg19: chr22-40307894;