NM_000063.6:c.890C>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000063.6(C2):​c.890C>T​(p.Thr297Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,770 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

C2
NM_000063.6 missense

Scores

1
11
6

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.94
Variant links:
Genes affected
C2 (HGNC:1248): (complement C2) Component C2 is a serum glycoprotein that functions as part of the classical pathway of the complement system. Activated C1 cleaves C2 into C2a and C2b. The serine proteinase C2a then combines with complement factor 4b to create the C3 or C5 convertase. Deficiency of C2 has been reported to associated with certain autoimmune diseases and SNPs in this gene have been associated with altered susceptibility to age-related macular degeneration. This gene localizes within the class III region of the MHC on the short arm of chromosome 6. Alternative splicing results in multiple transcript variants encoding distinct isoforms. Additional transcript variants have been described in publications but their full-length sequence has not been determined.[provided by RefSeq, Mar 2009]
C2-AS1 (HGNC:49464): (C2 antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
C2NM_000063.6 linkc.890C>T p.Thr297Ile missense_variant Exon 7 of 18 ENST00000299367.10 NP_000054.2 P06681-1Q5JP69Q53HP3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
C2ENST00000299367.10 linkc.890C>T p.Thr297Ile missense_variant Exon 7 of 18 1 NM_000063.6 ENSP00000299367.5 P06681-1
ENSG00000244255ENST00000456570.5 linkc.530-1356C>T intron_variant Intron 4 of 29 2 ENSP00000410815.1 B4E1Z4

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1460770
Hom.:
0
Cov.:
31
AF XY:
0.00000275
AC XY:
2
AN XY:
726694
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.56
BayesDel_addAF
Uncertain
0.051
T
BayesDel_noAF
Benign
-0.16
CADD
Uncertain
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.22
T;.;T;.
Eigen
Benign
0.16
Eigen_PC
Uncertain
0.23
FATHMM_MKL
Uncertain
0.76
D
LIST_S2
Uncertain
0.88
D;D;D;D
M_CAP
Pathogenic
0.44
D
MetaRNN
Uncertain
0.73
D;D;D;D
MetaSVM
Uncertain
-0.12
T
MutationAssessor
Benign
2.0
.;.;M;.
PROVEAN
Uncertain
-3.1
D;D;D;D
REVEL
Uncertain
0.53
Sift
Benign
0.037
D;D;D;D
Sift4G
Uncertain
0.059
T;T;D;D
Polyphen
0.55
P;P;P;.
Vest4
0.23
MutPred
0.71
.;.;Gain of sheet (P = 0.1945);.;
MVP
0.92
MPC
0.59
ClinPred
0.96
D
GERP RS
4.8
Varity_R
0.22
gMVP
0.68

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.27
Details are displayed if max score is > 0.2
DS_AG_spliceai
0.27
Position offset: 12

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-31903740; API