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GeneBe

rs2228570

chr12-47879112-A-Cchr12-47879112-A-Gchr12-47879112-A-T

Variant summary

Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PVS1PM2_Supporting

The NM_000376(VDR):c.2T>G(p.Met1?) variant causes a start lost change. The variant was absent in control chromosomes in GnomAD Genomes project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 30)

Consequence

VDR
NM_000376 start_lost

Scores

7
6
3

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.35

Links

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 9 ACMG points.

PVS1
?
Start lost variant, no new inframe start found.
PM2
?
Very rare variant; Number of alleles below threshold, Median coverage is 30.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
VDRNM_000376.3 linkuse as main transcriptc.2T>G p.Met1? start_lost 3/10 ENST00000549336.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
VDRENST00000549336.6 linkuse as main transcriptc.2T>G p.Met1? start_lost 3/101 NM_000376.3 P1P11473-1

Frequencies

GnomAD3 genomes
Cov.:
30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
0.45
D
BayesDel_noAF
Pathogenic
0.41
Cadd
Uncertain
25
Dann
Uncertain
0.99
DEOGEN2
Benign
0.35
T;T;T;.;T;T;.
Eigen
Uncertain
0.45
Eigen_PC
Uncertain
0.42
FATHMM_MKL
Uncertain
0.95
D
M_CAP
Pathogenic
0.41
D
MetaRNN
Pathogenic
0.99
D;D;D;D;D;D;D
MetaSVM
Pathogenic
0.82
D
MutationTaster
Benign
1.0
D;D;N;N;N
PrimateAI
Uncertain
0.59
T
PROVEAN
Benign
-0.19
N;N;N;N;N;N;N
REVEL
Pathogenic
0.70
Sift
Pathogenic
0.0
D;D;D;D;D;D;D
Sift4G
Uncertain
0.0030
D;D;D;T;.;D;.
Polyphen
0.97
D;D;D;.;.;.;.
Vest4
0.74
MutPred
0.98
Gain of solvent accessibility (P = 0.11);Gain of solvent accessibility (P = 0.11);Gain of solvent accessibility (P = 0.11);.;Gain of solvent accessibility (P = 0.11);Gain of solvent accessibility (P = 0.11);Gain of solvent accessibility (P = 0.11);
MVP
0.93
MPC
1.5
ClinPred
0.99
D
GERP RS
2.9
Varity_R
0.88
gMVP
0.55

Splicing

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: rs2228570; hg19: chr12-48272895;