Genetic Variant BCAS2:p.Thr4Ala (chr1-114581582-T-C) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_005872.3(BCAS2):c.10A>G(p.Thr4Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0079 in 1,599,124 control chromosomes in the GnomAD database, including 88 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0049 ( 6 hom., cov: 32)

Exomes 𝑓: 0.0082 ( 82 hom. )

Consequence

BCAS2
NM_005872.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.34

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]

BCAS2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007404268).

BP6

Variant 1-114581582-T-C is Benign according to our data. Variant chr1-114581582-T-C is described in ClinVar as [Benign]. Clinvar id is 779064.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCAS2	NM_005872.3 link	c.10A>G	p.Thr4Ala	missense_variant	Exon 1 of 7	ENST00000369541.4	NP_005863.1	O75934B2R7W3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BCAS2	ENST00000369541.4 link	c.10A>G	p.Thr4Ala	missense_variant	Exon 1 of 7	1	NM_005872.3	ENSP00000358554.3		O75934
BCAS2	ENST00000485021.1 link	n.48A>G		non_coding_transcript_exon_variant	Exon 1 of 6	2

Frequencies

GnomAD3 genomes

AF:

0.00488

AC:

742

AN:

152120

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00179

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00242

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000828

Gnomad FIN

AF:

0.00330

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00854

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00575

AC:

1324

AN:

230424

Hom.:

AF XY:

0.00567

AC XY:

709

AN XY:

124964

show subpopulations

Gnomad AFR exome

AF:

0.00134

Gnomad AMR exome

AF:

0.00266

Gnomad ASJ exome

AF:

0.000208

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000732

Gnomad FIN exome

AF:

0.00458

Gnomad NFE exome

AF:

0.0105

Gnomad OTH exome

AF:

0.00686

GnomAD4 exome

AF:

0.00822

AC:

11896

AN:

1446886

Hom.:

Cov.:

AF XY:

0.00797

AC XY:

5735

AN XY:

719302

show subpopulations

Gnomad4 AFR exome

AF:

0.00148

Gnomad4 AMR exome

AF:

0.00303

Gnomad4 ASJ exome

AF:

0.000348

Gnomad4 EAS exome

AF:

0.0000259

Gnomad4 SAS exome

AF:

0.000770

Gnomad4 FIN exome

AF:

0.00569

Gnomad4 NFE exome

AF:

0.00992

Gnomad4 OTH exome

AF:

0.00650

GnomAD4 genome

AF:

0.00487

AC:

742

AN:

152238

Hom.:

Cov.:

AF XY:

0.00404

AC XY:

301

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.00178

Gnomad4 AMR

AF:

0.00242

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000829

Gnomad4 FIN

AF:

0.00330

Gnomad4 NFE

AF:

0.00854

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00518

Hom.:

Bravo

AF:

0.00495

TwinsUK

AF:

0.00917

AC:

ALSPAC

AF:

0.00778

AC:

ESP6500AA

AF:

0.00250

AC:

ESP6500EA

AF:

0.00907

AC:

ExAC

AF:

0.00594

AC:

719

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jun 14, 2017

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.30

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.011

Eigen

Benign

-0.079

Eigen_PC

Benign

0.11

FATHMM_MKL

Benign

0.60

LIST_S2

Benign

0.74

MetaRNN

Benign

0.0074

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.8

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-0.69

REVEL

Benign

0.11

Sift

Benign

0.36

Sift4G

Benign

0.17

Polyphen

0.0

Vest4

0.52

MVP

0.68

MPC

1.0

ClinPred

0.10

GERP RS

5.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.23

gMVP

0.67

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over