3-179185476-C-T

Variant names:

• chr3-179185476-C-T
• rs2677760
• NM_006218.4:c.-76-13274C>T

Variant summary

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

The NM_006218.4(PIK3CA):​c.-76-13274C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.568 in 152,084 control chromosomes in the GnomAD database, including 25,741 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. The gene PIK3CA is included in the ClinGen Criteria Specification Registry.

• Frequency: Genomes: 𝑓 0.57 (25741 hom., cov: 32)
• Consequence: PIK3CA NM_006218.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.78
• Publications: 25 publications found

Genes affected

PIK3CA (HGNC:8975): (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) Phosphatidylinositol 3-kinase is composed of an 85 kDa regulatory subunit and a 110 kDa catalytic subunit. The protein encoded by this gene represents the catalytic subunit, which uses ATP to phosphorylate PtdIns, PtdIns4P and PtdIns(4,5)P2. This gene has been found to be oncogenic and has been implicated in cervical cancers. A pseudogene of this gene has been defined on chromosome 22. [provided by RefSeq, Apr 2016]

PIK3CA Gene-Disease associations (from GenCC):

• overgrowth syndrome and/or cerebral malformations due to abnormalities in MTOR pathway genes

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• megalencephaly-capillary malformation-polymicrogyria syndrome

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Genomics England PanelApp
• vascular malformation

  Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
• Cowden disease

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Cowden syndrome 5

  Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)
• hereditary breast carcinoma

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
• familial ovarian cancer

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Specifications for PIK3CA are available in the ClinGen Criteria Specification Registry and recommended for reference when assigning criteria.

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.747 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006218.4. 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
	PIK3CA	NM_006218.4	MANE Select	c.-76-13274C>T		intron	N/A	NP_006209.2	P42336

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIK3CA	ENST00000263967.4	TSL:2 MANE Select	c.-76-13274C>T		intron	N/A	ENSP00000263967.3	P42336
	PIK3CA	ENST00000955190.1		c.-76-13274C>T		intron	N/A	ENSP00000625249.1
	PIK3CA	ENST00000876545.1		c.-76-13274C>T		intron	N/A	ENSP00000546604.1

Frequencies

GnomAD3 genomes AF: 0.568 AC: 86258 AN: 151966 Hom.: 25706 Cov.: 32

Gnomad AFR AF: 0.754

Gnomad AMI AF: 0.738

Gnomad AMR AF: 0.508

Gnomad ASJ AF: 0.563

Gnomad EAS AF: 0.222

Gnomad SAS AF: 0.466

Gnomad FIN AF: 0.434

Gnomad MID AF: 0.661

Gnomad NFE AF: 0.519

Gnomad OTH AF: 0.578

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

GnomAD4 genome AF: 0.568 AC: 86351 AN: 152084 Hom.: 25741 Cov.: 32 AF XY: 0.559 AC XY: 41519 AN XY: 74310

African (AFR) AF: 0.754 AC: 31321 AN: 41518

American (AMR) AF: 0.508 AC: 7770 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.563 AC: 1952 AN: 3468

East Asian (EAS) AF: 0.222 AC: 1145 AN: 5166

South Asian (SAS) AF: 0.466 AC: 2239 AN: 4804

European-Finnish (FIN) AF: 0.434 AC: 4583 AN: 10552

Middle Eastern (MID) AF: 0.663 AC: 195 AN: 294

European-Non Finnish (NFE) AF: 0.519 AC: 35260 AN: 67970

Other (OTH) AF: 0.574 AC: 1213 AN: 2112

Alfa AF: 0.539 Hom.: 46774

Bravo AF: 0.583

Asia WGS AF: 0.363 AC: 1260 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.33
DANN	Benign	0.37
PhyloP100		-5.8
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2677760; hg19: chr3-178903264;