chr12-18282464-GCCC-G

Variant names:

• chr12-18282464-GCCC-G
• rs35277916
• NM_001288772.2:c.385_387delCCC

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 1P and 10B. PM4_Supporting BP6_Moderate BA1

The NM_001288772.2(PIK3C2G):​c.385_387delCCC​(p.Pro129del) variant causes a conservative inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.392 in 1,607,454 control chromosomes in the GnomAD database, including 126,344 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.35 (9525 hom., cov: 0)
  • Exomes 𝑓: 0.40 (116819 hom.)
• Consequence: PIK3C2G NM_001288772.2 conservative_inframe_deletion
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.60
• Publications: 12 publications found

Genes affected

PIK3C2G (HGNC:8973): (phosphatidylinositol-4-phosphate 3-kinase catalytic subunit type 2 gamma) The protein encoded by this gene belongs to the phosphoinositide 3-kinase (PI3K) family. PI3-kinases play roles in signaling pathways involved in cell proliferation, oncogenic transformation, cell survival, cell migration, and intracellular protein trafficking. This protein contains a lipid kinase catalytic domain as well as a C-terminal C2 domain, a characteristic of class II PI3-kinases. C2 domains act as calcium-dependent phospholipid binding motifs that mediate translocation of proteins to membranes, and may also mediate protein-protein interactions. This gene may play a role in several diseases, including type II diabetes. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]

RERGL (HGNC:26213): (RERG like) Predicted to enable G protein activity and GTP binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_001288772.2. Strenght limited to Supporting due to length of the change: 1aa.
• BP6: Variant 12-18282464-GCCC-G is Benign according to our data. Variant chr12-18282464-GCCC-G is described in ClinVar as Benign. ClinVar VariationId is 1258527.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.405 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001288772.2. 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
	PIK3C2G	NM_001288772.2	MANE Select	c.385_387delCCC	p.Pro129del	conservative_inframe_deletion	Exon 2 of 33	NP_001275701.1	O75747-1
	PIK3C2G	NM_004570.6		c.385_387delCCC	p.Pro129del	conservative_inframe_deletion	Exon 2 of 32	NP_004561.3	O75747-2
	PIK3C2G	NM_001288774.2		c.-275_-273delCCC		5_prime_UTR	Exon 2 of 33	NP_001275703.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIK3C2G	ENST00000538779.6	TSL:5 MANE Select	c.385_387delCCC	p.Pro129del	conservative_inframe_deletion	Exon 2 of 33	ENSP00000445381.1	O75747-1
	PIK3C2G	ENST00000546003.5	TSL:1	n.385_387delCCC		non_coding_transcript_exon	Exon 1 of 32	ENSP00000441618.1	F5GWG6
	PIK3C2G	ENST00000675017.1		c.385_387delCCC	p.Pro129del	conservative_inframe_deletion	Exon 2 of 33	ENSP00000501889.1	O75747-1

Frequencies

GnomAD3 genomes AF: 0.346 AC: 52513 AN: 151674 Hom.: 9526 Cov.: 0

Gnomad AFR AF: 0.218

Gnomad AMI AF: 0.503

Gnomad AMR AF: 0.369

Gnomad ASJ AF: 0.367

Gnomad EAS AF: 0.277

Gnomad SAS AF: 0.329

Gnomad FIN AF: 0.434

Gnomad MID AF: 0.299

Gnomad NFE AF: 0.409

Gnomad OTH AF: 0.364

GnomAD2 exomes AF: 0.376 AC: 93251 AN: 248102 AF XY: 0.376

Gnomad AFR exome AF: 0.214

Gnomad AMR exome AF: 0.387

Gnomad ASJ exome AF: 0.369

Gnomad EAS exome AF: 0.268

Gnomad FIN exome AF: 0.440

Gnomad NFE exome AF: 0.410

Gnomad OTH exome AF: 0.384

GnomAD4 exome AF: 0.396 AC: 576981 AN: 1455660 Hom.: 116819 AF XY: 0.395 AC XY: 286059 AN XY: 724392

African (AFR) AF: 0.214 AC: 7149 AN: 33388

American (AMR) AF: 0.385 AC: 17174 AN: 44638

Ashkenazi Jewish (ASJ) AF: 0.372 AC: 9694 AN: 26084

East Asian (EAS) AF: 0.257 AC: 10206 AN: 39656

South Asian (SAS) AF: 0.342 AC: 29468 AN: 86154

European-Finnish (FIN) AF: 0.434 AC: 23105 AN: 53200

Middle Eastern (MID) AF: 0.324 AC: 1861 AN: 5752

European-Non Finnish (NFE) AF: 0.412 AC: 455662 AN: 1106616

Other (OTH) AF: 0.377 AC: 22662 AN: 60172

GnomAD4 genome AF: 0.346 AC: 52513 AN: 151794 Hom.: 9525 Cov.: 0 AF XY: 0.345 AC XY: 25609 AN XY: 74156

African (AFR) AF: 0.217 AC: 9001 AN: 41442

American (AMR) AF: 0.369 AC: 5624 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.367 AC: 1273 AN: 3468

East Asian (EAS) AF: 0.276 AC: 1421 AN: 5152

South Asian (SAS) AF: 0.329 AC: 1585 AN: 4812

European-Finnish (FIN) AF: 0.434 AC: 4566 AN: 10516

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.409 AC: 27736 AN: 67874

Other (OTH) AF: 0.360 AC: 762 AN: 2114

Alfa AF: 0.381 Hom.: 2072

Bravo AF: 0.339

Asia WGS AF: 0.282 AC: 981 AN: 3478

EpiCase AF: 0.403

EpiControl AF: 0.409

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.6
Mutation Taster		=84/16	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: rs35277916; hg19: chr12-18435398; COSMIC: COSV56795329; COSMIC: COSV56795329;