17-75395064-A-G

Position:

• chr17-75395064-A-G

Variant summary

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

The NM_002086.5(GRB2):​c.-137-1299T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.668 in 152,010 control chromosomes in the GnomAD database, including 38,994 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 (38994 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: GRB2 NM_002086.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.14

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]

LOC124904060 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.941 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRB2	NM_002086.5	c.-137-1299T>C		intron_variant		ENST00000316804.10	NP_002077.1
GRB2	NM_203506.3	c.-137-1299T>C		intron_variant			NP_987102.1
LOC124904060	XR_007065909.1	n.619A>G		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRB2	ENST00000316804.10	c.-137-1299T>C		intron_variant		1	NM_002086.5	ENSP00000339007.4

Frequencies

GnomAD3 genomes AF: 0.668 AC: 101468 AN: 151890 Hom.: 38999 Cov.: 32

Gnomad AFR AF: 0.256

Gnomad AMI AF: 0.784

Gnomad AMR AF: 0.785

Gnomad ASJ AF: 0.714

Gnomad EAS AF: 0.963

Gnomad SAS AF: 0.736

Gnomad FIN AF: 0.885

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.826

Gnomad OTH AF: 0.683

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

GnomAD4 genome AF: 0.668 AC: 101469 AN: 152010 Hom.: 38994 Cov.: 32 AF XY: 0.677 AC XY: 50282 AN XY: 74316

Gnomad4 AFR AF: 0.256

Gnomad4 AMR AF: 0.785

Gnomad4 ASJ AF: 0.714

Gnomad4 EAS AF: 0.963

Gnomad4 SAS AF: 0.736

Gnomad4 FIN AF: 0.885

Gnomad4 NFE AF: 0.826

Gnomad4 OTH AF: 0.681

Alfa AF: 0.646 Hom.: 3235

Bravo AF: 0.642

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.67
DANN	Benign	0.62

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: rs4788891; hg19: chr17-73391145;