17-75351244-T-C

Variant names:

• chr17-75351244-T-C
• rs1369299
• NM_002086.5:c.79-18447A>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.79-18447A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.67 in 152,002 control chromosomes in the GnomAD database, including 39,327 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 0.67 (39327 hom., cov: 31)
• Consequence: GRB2 NM_002086.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.81
• Publications: 12 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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.888 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.79-18447A>G		intron	N/A	NP_002077.1
	GRB2	NM_203506.3		c.79-18447A>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.79-18447A>G		intron	N/A	ENSP00000339007.4
	GRB2	ENST00000392564.5	TSL:1	c.79-18447A>G		intron	N/A	ENSP00000376347.1
	GRB2	ENST00000392563.5	TSL:1	c.79-18447A>G		intron	N/A	ENSP00000376346.1

Frequencies

GnomAD3 genomes AF: 0.671 AC: 101883 AN: 151884 Hom.: 39337 Cov.: 31

Gnomad AFR AF: 0.259

Gnomad AMI AF: 0.812

Gnomad AMR AF: 0.744

Gnomad ASJ AF: 0.729

Gnomad EAS AF: 0.910

Gnomad SAS AF: 0.742

Gnomad FIN AF: 0.899

Gnomad MID AF: 0.668

Gnomad NFE AF: 0.841

Gnomad OTH AF: 0.679

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

GnomAD4 genome AF: 0.670 AC: 101876 AN: 152002 Hom.: 39327 Cov.: 31 AF XY: 0.678 AC XY: 50347 AN XY: 74292

African (AFR) AF: 0.259 AC: 10711 AN: 41420

American (AMR) AF: 0.744 AC: 11349 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.729 AC: 2530 AN: 3470

East Asian (EAS) AF: 0.910 AC: 4706 AN: 5172

South Asian (SAS) AF: 0.742 AC: 3576 AN: 4820

European-Finnish (FIN) AF: 0.899 AC: 9507 AN: 10580

Middle Eastern (MID) AF: 0.656 AC: 193 AN: 294

European-Non Finnish (NFE) AF: 0.841 AC: 57138 AN: 67964

Other (OTH) AF: 0.677 AC: 1429 AN: 2112

Alfa AF: 0.783 Hom.: 90388

Bravo AF: 0.641

Asia WGS AF: 0.740 AC: 2575 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.31
DANN	Benign	0.74
PhyloP100		-2.8
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: rs1369299; hg19: chr17-73347325;