17-75347998-A-G

Variant names:

• chr17-75347998-A-G
• rs12950752
• NM_002086.5:c.79-15201T>C

Variant summary

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

The NM_002086.5(GRB2):​c.79-15201T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.618 in 152,122 control chromosomes in the GnomAD database, including 33,280 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 (33280 hom., cov: 32)
• Consequence: GRB2 NM_002086.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0780
• Publications: 17 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 = 0.847 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRB2	NM_002086.5	c.79-15201T>C		intron_variant	Intron 2 of 5	ENST00000316804.10	NP_002077.1
GRB2	NM_203506.3	c.79-15201T>C		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.79-15201T>C		intron_variant	Intron 2 of 5	1	NM_002086.5	ENSP00000339007.4

Frequencies

GnomAD3 genomes AF: 0.618 AC: 93942 AN: 152004 Hom.: 33289 Cov.: 32

Gnomad AFR AF: 0.248

Gnomad AMI AF: 0.802

Gnomad AMR AF: 0.693

Gnomad ASJ AF: 0.582

Gnomad EAS AF: 0.867

Gnomad SAS AF: 0.682

Gnomad FIN AF: 0.845

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.768

Gnomad OTH AF: 0.602

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

GnomAD4 genome AF: 0.618 AC: 93938 AN: 152122 Hom.: 33280 Cov.: 32 AF XY: 0.626 AC XY: 46513 AN XY: 74348

African (AFR) AF: 0.247 AC: 10253 AN: 41498

American (AMR) AF: 0.693 AC: 10590 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.582 AC: 2020 AN: 3468

East Asian (EAS) AF: 0.868 AC: 4495 AN: 5180

South Asian (SAS) AF: 0.682 AC: 3287 AN: 4822

European-Finnish (FIN) AF: 0.845 AC: 8960 AN: 10598

Middle Eastern (MID) AF: 0.527 AC: 155 AN: 294

European-Non Finnish (NFE) AF: 0.768 AC: 52183 AN: 67970

Other (OTH) AF: 0.601 AC: 1265 AN: 2106

Alfa AF: 0.717 Hom.: 72124

Bravo AF: 0.593

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	-1.0
CADD	Benign	5.2
DANN	Benign	0.39
PhyloP100		0.078
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: rs12950752; hg19: chr17-73344079;