Genetic Variant BCAR1:p.Ala768Pro (chr16-75229822-C-G) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_014567.5(BCAR1):c.2302G>C(p.Ala768Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A768T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Consequence

BCAR1
NM_014567.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.629

Publications

0 publications found

Variant links:

Genes affected

BCAR1 (HGNC:971): (BCAR1 scaffold protein, Cas family member) The protein encoded by this gene is a member of the Crk-associated substrate (CAS) family of scaffold proteins, characterized by the presence of multiple protein-protein interaction domains and many serine and tyrosine phosphorylation sites. The encoded protein contains a Src-homology 3 (SH3) domain, a proline-rich domain, a substrate domain which contains 15 repeat of the YxxP consensus phosphorylation motif for Src family kinases, a serine-rich domain, and a bipartite Src-binding domain, which can bind both SH2 and SH3 domains. This adaptor protein functions in multiple cellular pathways, including in cell motility, apoptosis and cell cycle control. Dysregulation of this gene can have a wide range of effects, affecting different pathways, including cardiac development, vascular smooth muscle cells, liver and kidney function, endothelial migration, and cancer. [provided by RefSeq, Sep 2017]

BCAR1 links:

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ACMG classification

Classification was made for transcript

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_014567.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BCAR1	NM_014567.5	MANE Select	c.2302G>C	p.Ala768Pro	missense	Exon 7 of 7	NP_055382.2
BCAR1	NM_001170714.3		c.2440G>C	p.Ala814Pro	missense	Exon 8 of 8	NP_001164185.1	P56945-6
BCAR1	NM_001170715.3		c.2356G>C	p.Ala786Pro	missense	Exon 7 of 7	NP_001164186.1	P56945-7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BCAR1	ENST00000162330.10	TSL:1 MANE Select	c.2302G>C	p.Ala768Pro	missense	Exon 7 of 7	ENSP00000162330.5	P56945-1
BCAR1	ENST00000563038.5	TSL:1	n.1907G>C		non_coding_transcript_exon	Exon 3 of 3
BCAR1	ENST00000418647.7	TSL:2	c.2440G>C	p.Ala814Pro	missense	Exon 8 of 8	ENSP00000391669.3	P56945-6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.99

BayesDel_addAF

Benign

-0.098

BayesDel_noAF

Benign

-0.38

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.19

Eigen

Benign

-0.36

Eigen_PC

Benign

-0.48

FATHMM_MKL

Benign

0.35

LIST_S2

Uncertain

0.96

M_CAP

Benign

0.024

MetaRNN

Uncertain

0.57

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.9

PhyloP100

0.63

PrimateAI

Uncertain

0.67

PROVEAN

Uncertain

-2.8

REVEL

Benign

0.16

Sift

Uncertain

0.0060

Sift4G

Uncertain

0.015

Polyphen

1.0

Vest4

0.62

MutPred

0.51

Gain of loop (P = 0.0166)

MVP

0.63

MPC

0.56

ClinPred

0.96

GERP RS

3.6

Varity_R

0.87

gMVP

0.81

Mutation Taster

=51/49

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over