chr17-75340950-G-C

Variant names:

• chr17-75340950-G-C
• rs9912608
• NM_002086.5:c.79-8153C>G

Variant summary

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

The NM_002086.5(GRB2):​c.79-8153C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.596 in 151,986 control chromosomes in the GnomAD database, including 32,354 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 0.60 (32354 hom., cov: 31)
• Consequence: GRB2 NM_002086.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.465
• Publications: 10 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.845 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002086.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRB2	NM_002086.5	MANE Select	c.79-8153C>G		intron	N/A	NP_002077.1
	GRB2	NM_203506.3		c.79-8153C>G		intron	N/A	NP_987102.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRB2	ENST00000316804.10	TSL:1 MANE Select	c.79-8153C>G		intron	N/A	ENSP00000339007.4
	GRB2	ENST00000392564.5	TSL:1	c.79-8153C>G		intron	N/A	ENSP00000376347.1
	GRB2	ENST00000392563.5	TSL:1	c.79-8153C>G		intron	N/A	ENSP00000376346.1

Frequencies

GnomAD3 genomes AF: 0.596 AC: 90581 AN: 151868 Hom.: 32365 Cov.: 31

Gnomad AFR AF: 0.179

Gnomad AMI AF: 0.801

Gnomad AMR AF: 0.682

Gnomad ASJ AF: 0.582

Gnomad EAS AF: 0.866

Gnomad SAS AF: 0.633

Gnomad FIN AF: 0.846

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.767

Gnomad OTH AF: 0.588

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

GnomAD4 genome AF: 0.596 AC: 90567 AN: 151986 Hom.: 32354 Cov.: 31 AF XY: 0.604 AC XY: 44876 AN XY: 74310

African (AFR) AF: 0.179 AC: 7415 AN: 41404

American (AMR) AF: 0.682 AC: 10411 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.582 AC: 2018 AN: 3470

East Asian (EAS) AF: 0.866 AC: 4476 AN: 5166

South Asian (SAS) AF: 0.633 AC: 3043 AN: 4808

European-Finnish (FIN) AF: 0.846 AC: 8952 AN: 10586

Middle Eastern (MID) AF: 0.524 AC: 153 AN: 292

European-Non Finnish (NFE) AF: 0.767 AC: 52141 AN: 67984

Other (OTH) AF: 0.585 AC: 1229 AN: 2102

Alfa AF: 0.598 Hom.: 2447

Bravo AF: 0.570

Asia WGS AF: 0.641 AC: 2230 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.64
DANN	Benign	0.41
PhyloP100		-0.47
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: rs9912608; hg19: chr17-73337031;