chr12-109930396-G-A

Position:

• chr12-109930396-G-A

Variant summary

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

The NM_057169.5(GIT2):​c.*2582C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.238 in 153,620 control chromosomes in the GnomAD database, including 4,798 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 0.24 (4753 hom., cov: 32)
  • Exomes 𝑓: 0.24 (45 hom.)
• Consequence: GIT2 NM_057169.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.26

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:):

TCHP (HGNC:28135): (trichoplein keratin filament binding) Involved in apoptotic process; negative regulation of cell growth; and negative regulation of cilium assembly. Located in several cellular components, including apical cortex; cytoskeleton; and mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.453 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GIT2	NM_057169.5	c.*2582C>T		3_prime_UTR_variant	20/20	ENST00000355312.8	NP_476510.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GIT2	ENST00000355312.8	c.*2582C>T		3_prime_UTR_variant	20/20	1	NM_057169.5	ENSP00000347464.3

Frequencies

GnomAD3 genomes AF: 0.238 AC: 36198 AN: 151990 Hom.: 4751 Cov.: 32

Gnomad AFR AF: 0.149

Gnomad AMI AF: 0.232

Gnomad AMR AF: 0.266

Gnomad ASJ AF: 0.242

Gnomad EAS AF: 0.201

Gnomad SAS AF: 0.469

Gnomad FIN AF: 0.295

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.264

Gnomad OTH AF: 0.230

GnomAD4 exome AF: 0.243 AC: 367 AN: 1508 Hom.: 45 Cov.: 0 AF XY: 0.226 AC XY: 181 AN XY: 800

Gnomad4 AFR exome AF: 0.0714

Gnomad4 AMR exome AF: 0.227

Gnomad4 ASJ exome AF: 0.231

Gnomad4 EAS exome AF: 0.218

Gnomad4 SAS exome AF: 0.375

Gnomad4 FIN exome AF: 0.257

Gnomad4 NFE exome AF: 0.242

Gnomad4 OTH exome AF: 0.263

GnomAD4 genome AF: 0.238 AC: 36219 AN: 152112 Hom.: 4753 Cov.: 32 AF XY: 0.243 AC XY: 18093 AN XY: 74342

Gnomad4 AFR AF: 0.148

Gnomad4 AMR AF: 0.267

Gnomad4 ASJ AF: 0.242

Gnomad4 EAS AF: 0.201

Gnomad4 SAS AF: 0.470

Gnomad4 FIN AF: 0.295

Gnomad4 NFE AF: 0.264

Gnomad4 OTH AF: 0.231

Alfa AF: 0.259 Hom.: 12121

Bravo AF: 0.226

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.055
DANN	Benign	0.55
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs2292354; hg19: chr12-110368201;