17-75373341-C-T

Variant names:

• chr17-75373341-C-T
• rs959260
• NM_002086.5:c.78+20210G>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002086.5(GRB2):​c.78+20210G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.661 in 152,122 control chromosomes in the GnomAD database, including 38,220 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 0.66 (38217 hom., cov: 32)
  • Exomes 𝑓: 1.0 (3 hom.)
• Consequence: GRB2 NM_002086.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.913

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]

ENSG00000264853 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 = 0.889 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRB2	NM_002086.5	c.78+20210G>A		intron_variant	Intron 2 of 5	ENST00000316804.10	NP_002077.1
GRB2	NM_203506.3	c.78+20210G>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.78+20210G>A		intron_variant	Intron 2 of 5	1	NM_002086.5	ENSP00000339007.4

Frequencies

GnomAD3 genomes AF: 0.662 AC: 100552 AN: 151998 Hom.: 38228 Cov.: 32

Gnomad AFR AF: 0.257

Gnomad AMI AF: 0.785

Gnomad AMR AF: 0.739

Gnomad ASJ AF: 0.714

Gnomad EAS AF: 0.911

Gnomad SAS AF: 0.735

Gnomad FIN AF: 0.885

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.826

Gnomad OTH AF: 0.670

GnomAD4 exome AF: 1.00 AC: 6 AN: 6 Hom.: 3 Cov.: 0 AF XY: 1.00 AC XY: 4 AN XY: 4

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 1.00

GnomAD4 genome AF: 0.661 AC: 100544 AN: 152116 Hom.: 38217 Cov.: 32 AF XY: 0.669 AC XY: 49756 AN XY: 74374

Gnomad4 AFR AF: 0.257

Gnomad4 AMR AF: 0.739

Gnomad4 ASJ AF: 0.714

Gnomad4 EAS AF: 0.911

Gnomad4 SAS AF: 0.735

Gnomad4 FIN AF: 0.885

Gnomad4 NFE AF: 0.826

Gnomad4 OTH AF: 0.669

Alfa AF: 0.798 Hom.: 97342

Bravo AF: 0.633

Asia WGS AF: 0.738 AC: 2568 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	0.61
DANN	Benign	0.76

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

Publications

LitVar

Other links and lift over

dbSNP: rs959260; hg19: chr17-73369422;