NM_080491.3:c.1290T>C

Variant names:

• chr11-78225120-A-G
• rs1385600
• NM_080491.3:c.1290T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_080491.3(GAB2):​c.1290T>C​(p.Val430Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 1,608,886 control chromosomes in the GnomAD database, including 38,069 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 0.27 (6531 hom., cov: 32)
  • Exomes 𝑓: 0.19 (31538 hom.)
• Consequence: GAB2 NM_080491.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.25
• Publications: 49 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]

ENSG00000288538 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP7: Synonymous conserved (PhyloP=2.25 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.434 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.1290T>C	p.Val430Val	synonymous	Exon 5 of 10	NP_536739.1	Q9UQC2-1
	GAB2	NM_012296.4		c.1176T>C	p.Val392Val	synonymous	Exon 5 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.1290T>C	p.Val430Val	synonymous	Exon 5 of 10	ENSP00000354952.4	Q9UQC2-1
	GAB2	ENST00000340149.6	TSL:1	c.1176T>C	p.Val392Val	synonymous	Exon 5 of 10	ENSP00000343959.2	Q9UQC2-2
	ENSG00000288538	ENST00000656562.1		n.964A>G		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.268 AC: 40719 AN: 151916 Hom.: 6514 Cov.: 32

Gnomad AFR AF: 0.439

Gnomad AMI AF: 0.0669

Gnomad AMR AF: 0.280

Gnomad ASJ AF: 0.263

Gnomad EAS AF: 0.402

Gnomad SAS AF: 0.278

Gnomad FIN AF: 0.201

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.164

Gnomad OTH AF: 0.271

GnomAD2 exomes AF: 0.248 AC: 62319 AN: 251118 AF XY: 0.240

Gnomad AFR exome AF: 0.435

Gnomad AMR exome AF: 0.360

Gnomad ASJ exome AF: 0.252

Gnomad EAS exome AF: 0.386

Gnomad FIN exome AF: 0.193

Gnomad NFE exome AF: 0.166

Gnomad OTH exome AF: 0.217

GnomAD4 exome AF: 0.192 AC: 279641 AN: 1456850 Hom.: 31538 Cov.: 30 AF XY: 0.193 AC XY: 140049 AN XY: 724998

African (AFR) AF: 0.449 AC: 14939 AN: 33308

American (AMR) AF: 0.350 AC: 15622 AN: 44680

Ashkenazi Jewish (ASJ) AF: 0.252 AC: 6589 AN: 26102

East Asian (EAS) AF: 0.415 AC: 16443 AN: 39648

South Asian (SAS) AF: 0.289 AC: 24894 AN: 86142

European-Finnish (FIN) AF: 0.194 AC: 10331 AN: 53382

Middle Eastern (MID) AF: 0.304 AC: 1751 AN: 5764

European-Non Finnish (NFE) AF: 0.159 AC: 175934 AN: 1107604

Other (OTH) AF: 0.218 AC: 13138 AN: 60220

GnomAD4 genome AF: 0.268 AC: 40787 AN: 152036 Hom.: 6531 Cov.: 32 AF XY: 0.270 AC XY: 20071 AN XY: 74306

African (AFR) AF: 0.439 AC: 18197 AN: 41458

American (AMR) AF: 0.280 AC: 4281 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.263 AC: 912 AN: 3468

East Asian (EAS) AF: 0.403 AC: 2073 AN: 5150

South Asian (SAS) AF: 0.278 AC: 1338 AN: 4810

European-Finnish (FIN) AF: 0.201 AC: 2131 AN: 10588

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.164 AC: 11141 AN: 67958

Other (OTH) AF: 0.268 AC: 566 AN: 2114

Alfa AF: 0.207 Hom.: 13114

Bravo AF: 0.282

Asia WGS AF: 0.295 AC: 1024 AN: 3478

EpiCase AF: 0.165

EpiControl AF: 0.164

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	10
DANN	Benign	0.65
PhyloP100		2.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
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: rs1385600; hg19: chr11-77936166; COSMIC: COSV60868306; COSMIC: COSV60868306;