17-75319287-C-T

Position:

• chr17-75319287-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000316804.10(GRB2):​c.*1081G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.608 in 150,120 control chromosomes in the GnomAD database, including 31,773 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 0.61 (31627 hom., cov: 25)
  • Exomes 𝑓: 0.82 (146 hom.)
• Consequence: GRB2 ENST00000316804.10 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.597

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.32).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.824 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRB2	NM_002086.5	c.*1081G>A		3_prime_UTR_variant	6/6	ENST00000316804.10	NP_002077.1
GRB2	NM_203506.3	c.*1081G>A		3_prime_UTR_variant	5/5		NP_987102.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRB2	ENST00000316804.10	c.*1081G>A		3_prime_UTR_variant	6/6	1	NM_002086.5	ENSP00000339007	P1

Frequencies

GnomAD3 genomes AF: 0.608 AC: 90958 AN: 149578 Hom.: 31637 Cov.: 25

Gnomad AFR AF: 0.243

Gnomad AMI AF: 0.776

Gnomad AMR AF: 0.687

Gnomad ASJ AF: 0.568

Gnomad EAS AF: 0.845

Gnomad SAS AF: 0.670

Gnomad FIN AF: 0.833

Gnomad MID AF: 0.529

Gnomad NFE AF: 0.753

Gnomad OTH AF: 0.595

GnomAD4 exome AF: 0.817 AC: 356 AN: 436 Hom.: 146 Cov.: 0 AF XY: 0.824 AC XY: 216 AN XY: 262

Gnomad4 FIN exome AF: 0.815

Gnomad4 NFE exome AF: 1.00

Gnomad4 OTH exome AF: 0.833

GnomAD4 genome AF: 0.608 AC: 90947 AN: 149684 Hom.: 31627 Cov.: 25 AF XY: 0.615 AC XY: 44898 AN XY: 73000

Gnomad4 AFR AF: 0.243

Gnomad4 AMR AF: 0.687

Gnomad4 ASJ AF: 0.568

Gnomad4 EAS AF: 0.845

Gnomad4 SAS AF: 0.670

Gnomad4 FIN AF: 0.833

Gnomad4 NFE AF: 0.753

Gnomad4 OTH AF: 0.594

Alfa AF: 0.712 Hom.: 51910

Bravo AF: 0.582

Asia WGS AF: 0.672 AC: 2336 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
CADD	Benign	11
DANN	Benign	0.89
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs7219; hg19: chr17-73315368;