17-75325606-T-C

Variant names:

• chr17-75325606-T-C
• rs7207618
• NM_002086.5:c.299+292A>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.299+292A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.616 in 152,106 control chromosomes in the GnomAD database, including 32,549 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 0.62 (32549 hom., cov: 32)
• Consequence: GRB2 NM_002086.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.66
• Publications: 11 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.846 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRB2	NM_002086.5	c.299+292A>G		intron_variant	Intron 4 of 5	ENST00000316804.10	NP_002077.1
GRB2	NM_203506.3	c.177-3779A>G		intron_variant	Intron 3 of 4		NP_987102.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRB2	ENST00000316804.10	c.299+292A>G		intron_variant	Intron 4 of 5	1	NM_002086.5	ENSP00000339007.4

Frequencies

GnomAD3 genomes AF: 0.616 AC: 93632 AN: 151988 Hom.: 32556 Cov.: 32

Gnomad AFR AF: 0.271

Gnomad AMI AF: 0.778

Gnomad AMR AF: 0.689

Gnomad ASJ AF: 0.567

Gnomad EAS AF: 0.867

Gnomad SAS AF: 0.681

Gnomad FIN AF: 0.832

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.753

Gnomad OTH AF: 0.599

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

GnomAD4 genome AF: 0.616 AC: 93634 AN: 152106 Hom.: 32549 Cov.: 32 AF XY: 0.623 AC XY: 46356 AN XY: 74364

African (AFR) AF: 0.271 AC: 11229 AN: 41468

American (AMR) AF: 0.689 AC: 10521 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.567 AC: 1967 AN: 3470

East Asian (EAS) AF: 0.868 AC: 4484 AN: 5168

South Asian (SAS) AF: 0.680 AC: 3277 AN: 4820

European-Finnish (FIN) AF: 0.832 AC: 8809 AN: 10590

Middle Eastern (MID) AF: 0.520 AC: 153 AN: 294

European-Non Finnish (NFE) AF: 0.753 AC: 51228 AN: 68006

Other (OTH) AF: 0.598 AC: 1260 AN: 2108

Alfa AF: 0.712 Hom.: 9749

Bravo AF: 0.592

Asia WGS AF: 0.690 AC: 2399 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.42
DANN	Benign	0.36
PhyloP100		-2.7
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: rs7207618; hg19: chr17-73321687;