rs4766646

Positions:

• chr12-109960340-T-A
• chr12-109960340-T-C
• chr12-109960340-T-G

Variant summary

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

The NM_057169.5(GIT2):​c.988-382A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.727 in 152,208 control chromosomes in the GnomAD database, including 41,594 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 0.73 (41594 hom., cov: 33)
• Consequence: GIT2 NM_057169.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.581

Genes affected

GIT2 (HGNC:4273): (GIT ArfGAP 2) This gene encodes a member of the GIT protein family, which interact with G protein-coupled receptor kinases and possess ADP-ribosylation factor (ARF) GTPase-activating protein (GAP) activity. GIT proteins traffic between cytoplasmic complexes, focal adhesions, and the cell periphery, and interact with Pak interacting exchange factor beta (PIX) to form large oligomeric complexes that transiently recruit other proteins. GIT proteins regulate cytoskeletal dynamics and participate in receptor internalization and membrane trafficking. This gene has been shown to repress lamellipodial extension and focal adhesion turnover, and is thought to regulate cell motility. This gene undergoes extensive alternative splicing to generate multiple isoforms, but the full-length nature of some of these variants has not been determined. The various isoforms have functional differences, with respect to ARF GAP activity and to G protein-coupled receptor kinase 2 binding. [provided by RefSeq, Sep 2008]

TCHP (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.888 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GIT2	NM_057169.5	c.988-382A>T		intron_variant		ENST00000355312.8	NP_476510.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GIT2	ENST00000355312.8	c.988-382A>T		intron_variant		1	NM_057169.5	ENSP00000347464.3

Frequencies

GnomAD3 genomes AF: 0.727 AC: 110518 AN: 152088 Hom.: 41523 Cov.: 33

Gnomad AFR AF: 0.895

Gnomad AMI AF: 0.526

Gnomad AMR AF: 0.753

Gnomad ASJ AF: 0.538

Gnomad EAS AF: 0.340

Gnomad SAS AF: 0.799

Gnomad FIN AF: 0.702

Gnomad MID AF: 0.706

Gnomad NFE AF: 0.660

Gnomad OTH AF: 0.694

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

GnomAD4 genome AF: 0.727 AC: 110655 AN: 152208 Hom.: 41594 Cov.: 33 AF XY: 0.728 AC XY: 54169 AN XY: 74416

Gnomad4 AFR AF: 0.895

Gnomad4 AMR AF: 0.754

Gnomad4 ASJ AF: 0.538

Gnomad4 EAS AF: 0.339

Gnomad4 SAS AF: 0.799

Gnomad4 FIN AF: 0.702

Gnomad4 NFE AF: 0.660

Gnomad4 OTH AF: 0.694

Alfa AF: 0.593 Hom.: 1643

Bravo AF: 0.730

Asia WGS AF: 0.658 AC: 2291 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.38
DANN	Benign	0.66

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: rs4766646; hg19: chr12-110398145;