chr11-78216990-G-T

Variant names:

• chr11-78216990-G-T
• rs3740677
• NM_080491.3:c.*2282C>A

Variant summary

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

The NM_080491.3(GAB2):​c.*2282C>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 0.573 in 152,166 control chromosomes in the GnomAD database, including 29,140 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 0.57 (29105 hom., cov: 31)
  • Exomes 𝑓: 0.75 (35 hom.)
• Consequence: GAB2 NM_080491.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.482
• Publications: 23 publications found

Genes affected

GAB2 (HGNC:14458): (GRB2 associated binding protein 2) This gene is a member of the GRB2-associated binding protein (GAB) gene family. These proteins contain pleckstrin homology (PH) domain, and bind SHP2 tyrosine phosphatase and GRB2 adapter protein. They act as adapters for transmitting various signals in response to stimuli through cytokine and growth factor receptors, and T- and B-cell antigen receptors. The protein encoded by this gene is the principal activator of phosphatidylinositol-3 kinase in response to activation of the high affinity IgE receptor. Two alternatively spliced transcripts encoding different isoforms have been described for this gene. [provided by RefSeq, Nov 2009]

USP35 (HGNC:20061): (ubiquitin specific peptidase 35) This gene encodes a member of the peptidase C19 family of ubiquitin-specific proteases. These deubiquitinating enzymes (DUBs) catalyze the removal of ubiquitin proteins from other proteins. The encoded protein associates with polarized mitochondria and has been shown to inhibit NF-kappa B activation and delay PARK2-mediated degradation of mitochondria. Expression of this gene is upregulated by the let-7a microRNA and reduced expression has been observed in human tumor tissues. [provided by RefSeq, Jul 2017]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.77 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080491.3. 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
	GAB2	NM_080491.3	MANE Select	c.*2282C>A		3_prime_UTR	Exon 10 of 10	NP_536739.1	Q9UQC2-1
	GAB2	NM_012296.4		c.*2282C>A		3_prime_UTR	Exon 10 of 10	NP_036428.1	Q9UQC2-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GAB2	ENST00000361507.5	TSL:1 MANE Select	c.*2282C>A		3_prime_UTR	Exon 10 of 10	ENSP00000354952.4	Q9UQC2-1
	GAB2	ENST00000340149.6	TSL:1	c.*2282C>A		3_prime_UTR	Exon 10 of 10	ENSP00000343959.2	Q9UQC2-2

Frequencies

GnomAD3 genomes AF: 0.573 AC: 87059 AN: 151922 Hom.: 29108 Cov.: 31

Gnomad AFR AF: 0.248

Gnomad AMI AF: 0.890

Gnomad AMR AF: 0.608

Gnomad ASJ AF: 0.659

Gnomad EAS AF: 0.257

Gnomad SAS AF: 0.407

Gnomad FIN AF: 0.661

Gnomad MID AF: 0.650

Gnomad NFE AF: 0.775

Gnomad OTH AF: 0.594

GnomAD4 exome AF: 0.746 AC: 94 AN: 126 Hom.: 35 Cov.: 0 AF XY: 0.745 AC XY: 70 AN XY: 94

African (AFR) AF: 0.250 AC: 2 AN: 8

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.250 AC: 1 AN: 4

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.250 AC: 1 AN: 4

European-Finnish (FIN) AF: 0.750 AC: 9 AN: 12

Middle Eastern (MID) AF: 1.00 AC: 2 AN: 2

European-Non Finnish (NFE) AF: 0.826 AC: 76 AN: 92

Other (OTH) AF: 0.750 AC: 3 AN: 4

GnomAD4 genome AF: 0.573 AC: 87060 AN: 152040 Hom.: 29105 Cov.: 31 AF XY: 0.565 AC XY: 41982 AN XY: 74336

African (AFR) AF: 0.247 AC: 10247 AN: 41446

American (AMR) AF: 0.608 AC: 9291 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.659 AC: 2284 AN: 3464

East Asian (EAS) AF: 0.257 AC: 1328 AN: 5176

South Asian (SAS) AF: 0.410 AC: 1975 AN: 4822

European-Finnish (FIN) AF: 0.661 AC: 6989 AN: 10566

Middle Eastern (MID) AF: 0.634 AC: 185 AN: 292

European-Non Finnish (NFE) AF: 0.775 AC: 52708 AN: 67972

Other (OTH) AF: 0.590 AC: 1243 AN: 2108

Alfa AF: 0.712 Hom.: 63016

Bravo AF: 0.557

Asia WGS AF: 0.310 AC: 1080 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.3
DANN	Benign	0.69
PhyloP100		0.48
Mutation Taster		=99/1	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: rs3740677; hg19: chr11-77928036;