chr1-114575611-T-C

Variant names:

• chr1-114575611-T-C
• NM_005872.3:c.398A>G

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.17
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005872.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCAS2	NM_005872.3	MANE Select	c.398A>G	p.Asn133Ser	missense	Exon 4 of 7	NP_005863.1	O75934

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCAS2	ENST00000369541.4	TSL:1 MANE Select	c.398A>G	p.Asn133Ser	missense	Exon 4 of 7	ENSP00000358554.3	O75934
	BCAS2	ENST00000886260.1		c.500A>G	p.Asn167Ser	missense	Exon 5 of 8	ENSP00000556319.1
	BCAS2	ENST00000968205.1		c.455A>G	p.Asn152Ser	missense	Exon 4 of 7	ENSP00000638264.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		7.2
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
Mutation Taster		=69/31	polymorphism

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

Other links and lift over

hg19: chr1-115118232;