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17-74843140-G-A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_000835.6(GRIN2C):c.2997C>T(p.Ala999=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00127 in 418,078 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0017 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0011 ( 1 hom. )

Consequence

GRIN2C
NM_000835.6 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.13
Variant links:
Genes affected
GRIN2C (HGNC:4587): (glutamate ionotropic receptor NMDA type subunit 2C) This gene encodes a subunit of the N-methyl-D-aspartate (NMDA) receptor, which is a subtype of ionotropic glutamate receptor. NMDA receptors are found in the central nervous system, are permeable to cations and have an important role in physiological processes such as learning, memory, and synaptic development. The receptor is a tetramer of different subunits (typically heterodimer of subunit 1 with one or more of subunits 2A-D), forming a channel that is permeable to calcium, potassium, and sodium, and whose properties are determined by subunit composition. Alterations in the subunit composition of the receptor are associated with pathophysiological conditions such as Parkinson's disease, Alzheimer's disease, depression, and schizophrenia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2013]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PM2
?
    PM2 - Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
Very rare variant in population databases, with high coverage;
BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.87).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 17-74843140-G-A is Benign according to our data. Variant chr17-74843140-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 769927.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=1.13 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
GRIN2CNM_000835.6 linkuse as main transcriptc.2997C>T p.Ala999= synonymous_variant 13/13 ENST00000293190.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GRIN2CENST00000293190.10 linkuse as main transcriptc.2997C>T p.Ala999= synonymous_variant 13/131 NM_000835.6 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00165
AC:
251
AN:
151694
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00157
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00677
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.000962
Gnomad MID
AF:
0.00955
Gnomad NFE
AF:
0.00100
Gnomad OTH
AF:
0.000960
GnomAD3 exomes
AF:
0.00152
AC:
1
AN:
658
Hom.:
0
AF XY:
0.00256
AC XY:
1
AN XY:
390
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00467
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00106
AC:
281
AN:
266276
Hom.:
1
Cov.:
3
AF XY:
0.00110
AC XY:
151
AN XY:
136678
show subpopulations
Gnomad4 AFR exome
AF:
0.00158
Gnomad4 AMR exome
AF:
0.00178
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000117
Gnomad4 FIN exome
AF:
0.000521
Gnomad4 NFE exome
AF:
0.00119
Gnomad4 OTH exome
AF:
0.00193
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00165
AC:
251
AN:
151802
Hom.:
0
Cov.:
33
AF XY:
0.00193
AC XY:
143
AN XY:
74238
show subpopulations
Gnomad4 AFR
AF:
0.00157
Gnomad4 AMR
AF:
0.00676
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.000962
Gnomad4 NFE
AF:
0.00100
Gnomad4 OTH
AF:
0.000950
Alfa
AF:
0.000847
Hom.:
0
Bravo
AF:
0.00151
Asia WGS
AF:
0.000293
AC:
1
AN:
3424

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingInvitaeMay 07, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.87
Cadd
Benign
6.5
Dann
Benign
0.96

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

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

Other links and lift over

dbSNP: rs563639617; hg19: chr17-72839279; API