rs16967789

Positions:

• chr17-75332908-G-A

Variant summary

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

The NM_002086.5(GRB2):​c.79-111C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 645,562 control chromosomes in the GnomAD database, including 7,832 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 0.17 (2460 hom., cov: 32)
  • Exomes 𝑓: 0.13 (5372 hom.)
• Consequence: GRB2 NM_002086.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.561

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.264 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRB2	NM_002086.5	c.79-111C>T		intron_variant		ENST00000316804.10	NP_002077.1
GRB2	NM_203506.3	c.79-111C>T		intron_variant			NP_987102.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRB2	ENST00000316804.10	c.79-111C>T		intron_variant		1	NM_002086.5	ENSP00000339007.4

Frequencies

GnomAD3 genomes AF: 0.166 AC: 25212 AN: 152054 Hom.: 2446 Cov.: 32

Gnomad AFR AF: 0.268

Gnomad AMI AF: 0.0450

Gnomad AMR AF: 0.119

Gnomad ASJ AF: 0.272

Gnomad EAS AF: 0.0425

Gnomad SAS AF: 0.190

Gnomad FIN AF: 0.101

Gnomad MID AF: 0.242

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.185

GnomAD4 exome AF: 0.134 AC: 65921 AN: 493390 Hom.: 5372 AF XY: 0.137 AC XY: 36150 AN XY: 264418

Gnomad4 AFR exome AF: 0.265

Gnomad4 AMR exome AF: 0.0854

Gnomad4 ASJ exome AF: 0.267

Gnomad4 EAS exome AF: 0.0253

Gnomad4 SAS exome AF: 0.185

Gnomad4 FIN exome AF: 0.103

Gnomad4 NFE exome AF: 0.128

Gnomad4 OTH exome AF: 0.147

GnomAD4 genome AF: 0.166 AC: 25252 AN: 152172 Hom.: 2460 Cov.: 32 AF XY: 0.164 AC XY: 12198 AN XY: 74404

Gnomad4 AFR AF: 0.268

Gnomad4 AMR AF: 0.119

Gnomad4 ASJ AF: 0.272

Gnomad4 EAS AF: 0.0422

Gnomad4 SAS AF: 0.190

Gnomad4 FIN AF: 0.101

Gnomad4 NFE AF: 0.127

Gnomad4 OTH AF: 0.188

Alfa AF: 0.146 Hom.: 2359

Bravo AF: 0.168

Asia WGS AF: 0.167 AC: 580 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.0
DANN	Benign	0.66

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: rs16967789; hg19: chr17-73328989;