NM_005872.3:c.398A>G

Variant summary

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

The NM_005872.3(BCAS2):​c.398A>G​(p.Asn133Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Consequence

BCAS2
NM_005872.3 missense

Scores

1
7
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.17
Variant links:
Genes affected
BCAS2 (HGNC:975): (BCAS2 pre-mRNA processing factor) Involved in mRNA splicing, via spliceosome. Located in centrosome and nuclear speck. Part of U2-type catalytic step 2 spliceosome. Colocalizes with DNA replication factor A complex. Implicated in breast cancer. [provided by Alliance of Genome Resources, Apr 2022]

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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
BCAS2NM_005872.3 linkc.398A>G p.Asn133Ser missense_variant Exon 4 of 7 ENST00000369541.4 NP_005863.1 O75934B2R7W3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
BCAS2ENST00000369541.4 linkc.398A>G p.Asn133Ser missense_variant Exon 4 of 7 1 NM_005872.3 ENSP00000358554.3 O75934
BCAS2ENST00000485021.1 linkn.365A>G non_coding_transcript_exon_variant Exon 3 of 6 2

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
31

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Apr 25, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.398A>G (p.N133S) alteration is located in exon 4 (coding exon 4) of the BCAS2 gene. This alteration results from a A to G substitution at nucleotide position 398, causing the asparagine (N) at amino acid position 133 to be replaced by a serine (S). 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
0.099
BayesDel_addAF
Benign
-0.11
T
BayesDel_noAF
Benign
-0.40
CADD
Benign
21
DANN
Uncertain
0.99
DEOGEN2
Benign
0.053
T
Eigen
Uncertain
0.20
Eigen_PC
Uncertain
0.35
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.96
D
M_CAP
Benign
0.0051
T
MetaRNN
Uncertain
0.58
D
MetaSVM
Benign
-0.89
T
MutationAssessor
Uncertain
2.5
M
PrimateAI
Uncertain
0.71
T
PROVEAN
Benign
-1.6
N
REVEL
Benign
0.19
Sift
Benign
0.13
T
Sift4G
Benign
0.21
T
Polyphen
0.19
B
Vest4
0.87
MutPred
0.55
Loss of methylation at K136 (P = 0.1334);
MVP
0.64
MPC
0.27
ClinPred
0.89
D
GERP RS
5.6
Varity_R
0.47
gMVP
0.42

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
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: chr1-115118232; API