17-8369519-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001304947.3(KRBA2):​c.848G>C​(p.Ser283Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S283N) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Consequence

KRBA2
NM_001304947.3 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.292
Variant links:
Genes affected
KRBA2 (HGNC:26989): (KRAB-A domain containing 2) Predicted to enable nucleic acid binding activity. Predicted to be involved in DNA integration and regulation of transcription, DNA-templated. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.067406446).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
KRBA2NM_001304947.3 linkc.848G>C p.Ser283Thr missense_variant Exon 2 of 2 ENST00000396267.3 NP_001291876.1 Q6ZNG9A8MX02
KRBA2NM_213597.3 linkc.1094G>C p.Ser365Thr missense_variant Exon 2 of 2 NP_998762.1 Q6ZNG9

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
KRBA2ENST00000396267.3 linkc.848G>C p.Ser283Thr missense_variant Exon 2 of 2 2 NM_001304947.3 ENSP00000379565.3 A8MX02
ENSG00000263809ENST00000582471.1 linkn.*1831G>C non_coding_transcript_exon_variant Exon 6 of 6 5 ENSP00000463847.1 J3QQQ9
ENSG00000263809ENST00000582471.1 linkn.*1831G>C 3_prime_UTR_variant Exon 6 of 6 5 ENSP00000463847.1 J3QQQ9

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
33
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Aug 19, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1094G>C (p.S365T) alteration is located in exon 2 (coding exon 2) of the KRBA2 gene. This alteration results from a G to C substitution at nucleotide position 1094, causing the serine (S) at amino acid position 365 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.094
BayesDel_addAF
Benign
-0.23
T
BayesDel_noAF
Benign
-0.56
CADD
Benign
2.5
DANN
Benign
0.42
DEOGEN2
Benign
0.024
.;T;T;T;.
Eigen
Benign
-1.6
Eigen_PC
Benign
-1.8
FATHMM_MKL
Benign
0.012
N
LIST_S2
Benign
0.52
.;T;T;.;T
M_CAP
Benign
0.0015
T
MetaRNN
Benign
0.067
T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.9
.;.;M;M;.
PrimateAI
Benign
0.30
T
PROVEAN
Benign
-0.79
.;N;N;.;.
REVEL
Benign
0.069
Sift
Benign
0.21
.;T;T;.;.
Sift4G
Benign
0.48
.;T;T;.;.
Polyphen
0.33
.;.;B;B;.
Vest4
0.28, 0.27
MutPred
0.32
.;.;Loss of disorder (P = 0.0659);Loss of disorder (P = 0.0659);.;
MVP
0.13
MPC
0.14
ClinPred
0.14
T
GERP RS
-5.5
Varity_R
0.057
gMVP
0.28

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-8272837; API