rs4350602

Variant names:

• chr17-75359688-C-T
• rs4350602
• NM_002086.5:c.79-26891G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002086.5(GRB2):​c.79-26891G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.563 in 151,740 control chromosomes in the GnomAD database, including 29,201 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 0.56 (29201 hom., cov: 29)
• Consequence: GRB2 NM_002086.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.630
• Publications: 13 publications found

Genes affected

GRB2 (HGNC:4566): (growth factor receptor bound protein 2) The protein encoded by this gene binds the epidermal growth factor receptor and contains one SH2 domain and two SH3 domains. Its two SH3 domains direct complex formation with proline-rich regions of other proteins, and its SH2 domain binds tyrosine phosphorylated sequences. This gene is similar to the Sem5 gene of C.elegans, which is involved in the signal transduction pathway. Two alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ENSG00000265987 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.844 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRB2	NM_002086.5	c.79-26891G>A		intron_variant	Intron 2 of 5	ENST00000316804.10	NP_002077.1
GRB2	NM_203506.3	c.79-26891G>A		intron_variant	Intron 2 of 4		NP_987102.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRB2	ENST00000316804.10	c.79-26891G>A		intron_variant	Intron 2 of 5	1	NM_002086.5	ENSP00000339007.4

Frequencies

GnomAD3 genomes AF: 0.564 AC: 85492 AN: 151622 Hom.: 29213 Cov.: 29

Gnomad AFR AF: 0.156

Gnomad AMI AF: 0.796

Gnomad AMR AF: 0.652

Gnomad ASJ AF: 0.572

Gnomad EAS AF: 0.864

Gnomad SAS AF: 0.623

Gnomad FIN AF: 0.792

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.726

Gnomad OTH AF: 0.553

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

GnomAD4 genome AF: 0.563 AC: 85474 AN: 151740 Hom.: 29201 Cov.: 29 AF XY: 0.570 AC XY: 42299 AN XY: 74154

African (AFR) AF: 0.155 AC: 6427 AN: 41360

American (AMR) AF: 0.652 AC: 9926 AN: 15214

Ashkenazi Jewish (ASJ) AF: 0.572 AC: 1983 AN: 3466

East Asian (EAS) AF: 0.865 AC: 4462 AN: 5160

South Asian (SAS) AF: 0.622 AC: 2985 AN: 4796

European-Finnish (FIN) AF: 0.792 AC: 8324 AN: 10512

Middle Eastern (MID) AF: 0.517 AC: 152 AN: 294

European-Non Finnish (NFE) AF: 0.726 AC: 49335 AN: 67930

Other (OTH) AF: 0.551 AC: 1157 AN: 2100

Alfa AF: 0.621 Hom.: 4316

Bravo AF: 0.540

Asia WGS AF: 0.632 AC: 2199 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.94
DANN	Benign	0.49
PhyloP100		-0.63
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4350602; hg19: chr17-73355769;