NM_014567.5:c.2302G>C

Variant names:

• chr16-75229822-C-G
• rs111683417
• NM_014567.5:c.2302G>C

Variant summary

Our verdict is Uncertain significance. Variant got 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.

• Frequency: Genomes: not found (cov: 33)
• Consequence: BCAR1 NM_014567.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.629

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]

ACMG classification

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
BCAR1	NM_014567.5	c.2302G>C	p.Ala768Pro	missense_variant	Exon 7 of 7	ENST00000162330.10	NP_055382.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BCAR1	ENST00000162330.10	c.2302G>C	p.Ala768Pro	missense_variant	Exon 7 of 7	1	NM_014567.5	ENSP00000162330.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Benign	-0.098	T
BayesDel_noAF	Benign	-0.38
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.19	.;T;.;.;.;.;.;.
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.48
FATHMM_MKL	Benign	0.35	N
LIST_S2	Uncertain	0.96	D;D;D;D;D;D;D;D
M_CAP	Benign	0.024	T
MetaRNN	Uncertain	0.57	D;D;D;D;D;D;D;D
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.9	.;L;.;L;.;.;.;.
PrimateAI	Uncertain	0.67	T
PROVEAN	Uncertain	-2.8	D;D;D;D;D;D;D;D
REVEL	Benign	0.16
Sift	Uncertain	0.0060	D;D;D;D;D;D;D;D
Sift4G	Uncertain	0.015	D;D;D;D;D;D;D;D
Polyphen		1.0	.;D;.;.;.;.;.;.
Vest4		0.62
MutPred		0.51		.;Gain of loop (P = 0.0166);.;Gain of loop (P = 0.0166);.;.;.;.;
MVP		0.63
MPC		0.56
ClinPred		0.96	D
GERP RS		3.6
Varity_R		0.87
gMVP		0.81

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

LitVar

Other links and lift over

dbSNP: rs111683417; hg19: chr16-75263720;