20-53953573-C-A

Position:

• chr20-53953573-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001366298.2(BCAS1):​c.1674G>T​(p.Lys558Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: BCAS1 NM_001366298.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0870

Genes affected

BCAS1 (HGNC:974): (brain enriched myelin associated protein 1) This gene resides in a region at 20q13 which is amplified in a variety of tumor types and associated with more aggressive tumor phenotypes. Among the genes identified from this region, it was found to be highly expressed in three amplified breast cancer cell lines and in one breast tumor without amplification at 20q13.2. However, this gene is not in the common region of maximal amplification and its expression was not detected in the breast cancer cell line MCF7, in which this region is highly amplified. Although not consistently expressed, this gene is a candidate oncogene. [provided by RefSeq, Apr 2016]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18530357).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BCAS1	NM_001366298.2	c.1674G>T	p.Lys558Asn	missense_variant	12/13	ENST00000688948.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BCAS1	ENST00000688948.1	c.1674G>T	p.Lys558Asn	missense_variant	12/13		NM_001366298.2	A2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 10, 2024

The c.1539G>T (p.K513N) alteration is located in exon 11 (coding exon 10) of the BCAS1 gene. This alteration results from a G to T substitution at nucleotide position 1539, causing the lysine (K) at amino acid position 513 to be replaced by an asparagine (N). 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	Uncertain	0.44
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.21	T;.;T
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.54
FATHMM_MKL	Benign	0.26	N
LIST_S2	Uncertain	0.90	D;D;D
M_CAP	Benign	0.041	D
MetaRNN	Benign	0.19	T;T;T
MetaSVM	Benign	-0.77	T
MutationAssessor	Uncertain	2.3	.;.;M
MutationTaster	Benign	0.80	D;D;N;N
PrimateAI	Benign	0.45	T
PROVEAN	Pathogenic	-4.6	D;D;D
REVEL	Benign	0.10
Sift	Pathogenic	0.0	D;D;D
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		1.0, 1.0	.;D;D
Vest4		0.34, 0.32
MutPred		0.45		.;.;Loss of methylation at K513 (P = 0.0028);
MVP		0.40
MPC		0.49
ClinPred		0.99	D
GERP RS		3.0
Varity_R		0.57
gMVP		0.11

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-52570112;