16-81927353-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.554
Variant links:
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]

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ACMG classification

Classification made for transcript

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
PLCG2NM_002661.5 linkc.2514+175G>C intron_variant Intron 23 of 32 ENST00000564138.6 NP_002652.2 P16885
PLCG2NM_001425749.1 linkc.2514+175G>C intron_variant Intron 24 of 33 NP_001412678.1
PLCG2NM_001425750.1 linkc.2514+175G>C intron_variant Intron 23 of 32 NP_001412679.1
PLCG2NM_001425751.1 linkc.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
PLCG2ENST00000564138.6 linkc.2514+175G>C intron_variant Intron 23 of 32 1 NM_002661.5 ENSP00000482457.1 P16885

Frequencies

GnomAD3 genomes
AF:
0.159
AC:
24173
AN:
152018
Hom.:
2458
Cov.:
31
show subpopulations
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
show subpopulations
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
LINK: link

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs3813009; hg19: chr16-81960958; API