rs16967789

Variant names:

• chr17-75332908-G-A
• rs16967789
• NM_002086.5:c.79-111C>T

Variant summary

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

The NM_002086.5(GRB2):​c.79-111C>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
• Publications: 24 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]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002086.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRB2	NM_002086.5	MANE Select	c.79-111C>T		intron	N/A	NP_002077.1	B0LPF3
	GRB2	NM_203506.3		c.79-111C>T		intron	N/A	NP_987102.1	P62993-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRB2	ENST00000316804.10	TSL:1 MANE Select	c.79-111C>T		intron	N/A	ENSP00000339007.4	P62993-1
	GRB2	ENST00000392564.5	TSL:1	c.79-111C>T		intron	N/A	ENSP00000376347.1	P62993-1
	GRB2	ENST00000392563.5	TSL:1	c.79-111C>T		intron	N/A	ENSP00000376346.1	P62993-2

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

African (AFR) AF: 0.265 AC: 3263 AN: 12320

American (AMR) AF: 0.0854 AC: 1595 AN: 18670

Ashkenazi Jewish (ASJ) AF: 0.267 AC: 4222 AN: 15808

East Asian (EAS) AF: 0.0253 AC: 746 AN: 29442

South Asian (SAS) AF: 0.185 AC: 8918 AN: 48098

European-Finnish (FIN) AF: 0.103 AC: 3499 AN: 34052

Middle Eastern (MID) AF: 0.267 AC: 595 AN: 2228

European-Non Finnish (NFE) AF: 0.128 AC: 39119 AN: 305894

Other (OTH) AF: 0.147 AC: 3964 AN: 26878

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

African (AFR) AF: 0.268 AC: 11133 AN: 41496

American (AMR) AF: 0.119 AC: 1817 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.272 AC: 945 AN: 3470

East Asian (EAS) AF: 0.0422 AC: 219 AN: 5184

South Asian (SAS) AF: 0.190 AC: 915 AN: 4816

European-Finnish (FIN) AF: 0.101 AC: 1073 AN: 10608

Middle Eastern (MID) AF: 0.247 AC: 72 AN: 292

European-Non Finnish (NFE) AF: 0.127 AC: 8641 AN: 68008

Other (OTH) AF: 0.188 AC: 396 AN: 2106

Alfa AF: 0.145 Hom.: 3305

Bravo AF: 0.168

Asia WGS AF: 0.167 AC: 580 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.0
DANN	Benign	0.66
PhyloP100		0.56
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: rs16967789; hg19: chr17-73328989;