16-81927353-G-C

Variant names:

• chr16-81927353-G-C
• rs3813009
• NM_002661.5:c.2514+175G>C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002661.5(PLCG2):​c.2514+175G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 152,136 control chromosomes in the GnomAD database, including 2,457 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.16 (2457 hom., cov: 31)
• Consequence: PLCG2 NM_002661.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.554

Genes affected

PLCG2 (HGNC:9066): (phospholipase C gamma 2) The protein encoded by this gene is a transmembrane signaling enzyme that catalyzes the conversion of 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate to 1D-myo-inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG) using calcium as a cofactor. IP3 and DAG are second messenger molecules important for transmitting signals from growth factor receptors and immune system receptors across the cell membrane. Mutations in this gene have been found in autoinflammation, antibody deficiency, and immune dysregulation syndrome and familial cold autoinflammatory syndrome 3. [provided by RefSeq, Mar 2014]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 16-81927353-G-C is Benign according to our data. Variant chr16-81927353-G-C is described in ClinVar as [Benign]. Clinvar id is 1183021.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.221 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLCG2	NM_002661.5	c.2514+175G>C		intron_variant	Intron 23 of 32	ENST00000564138.6	NP_002652.2
PLCG2	NM_001425749.1	c.2514+175G>C		intron_variant	Intron 24 of 33		NP_001412678.1
PLCG2	NM_001425750.1	c.2514+175G>C		intron_variant	Intron 23 of 32		NP_001412679.1
PLCG2	NM_001425751.1	c.2514+175G>C		intron_variant	Intron 24 of 33		NP_001412680.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLCG2	ENST00000564138.6	c.2514+175G>C		intron_variant	Intron 23 of 32	1	NM_002661.5	ENSP00000482457.1

Frequencies

GnomAD3 genomes AF: 0.159 AC: 24173 AN: 152018 Hom.: 2458 Cov.: 31

Gnomad AFR AF: 0.0570

Gnomad AMI AF: 0.314

Gnomad AMR AF: 0.132

Gnomad ASJ AF: 0.231

Gnomad EAS AF: 0.0281

Gnomad SAS AF: 0.101

Gnomad FIN AF: 0.233

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.224

Gnomad OTH AF: 0.156

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

GnomAD4 genome AF: 0.159 AC: 24171 AN: 152136 Hom.: 2457 Cov.: 31 AF XY: 0.157 AC XY: 11642 AN XY: 74388

Gnomad4 AFR AF: 0.0568

Gnomad4 AMR AF: 0.132

Gnomad4 ASJ AF: 0.231

Gnomad4 EAS AF: 0.0281

Gnomad4 SAS AF: 0.102

Gnomad4 FIN AF: 0.233

Gnomad4 NFE AF: 0.224

Gnomad4 OTH AF: 0.156

Alfa AF: 0.191 Hom.: 395

Bravo AF: 0.147

Asia WGS AF: 0.0810 AC: 283 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 14, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.3
DANN	Benign	0.53

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

Publications

LitVar

Other links and lift over

dbSNP: rs3813009; hg19: chr16-81960958;