17-42816017-G-C

Variant names:

• chr17-42816017-G-C
• NM_001313998.2:c.721C>G

Variant summary

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

The NM_001313998.2(BECN1):​c.721C>G​(p.Leu241Val) 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: BECN1 NM_001313998.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.38

Genes affected

BECN1 (HGNC:1034): (beclin 1) This gene encodes a protein that regulates autophagy, a catabolic process of degradation induced by starvation. The encoded protein is a component of the phosphatidylinositol-3-kinase (PI3K) complex which mediates vesicle-trafficking processes. This protein is thought to play a role in multiple cellular processes, including tumorigenesis, neurodegeneration and apoptosis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2015]

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
BECN1	NM_001313998.2	c.721C>G	p.Leu241Val	missense_variant	Exon 8 of 12	ENST00000590099.6	NP_001300927.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BECN1	ENST00000590099.6	c.721C>G	p.Leu241Val	missense_variant	Exon 8 of 12	1	NM_001313998.2	ENSP00000465364.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 13, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.721C>G (p.L241V) alteration is located in exon 8 (coding exon 7) of the BECN1 gene. This alteration results from a C to G substitution at nucleotide position 721, causing the leucine (L) at amino acid position 241 to be replaced by a valine (V). 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	Benign	0.17
BayesDel_addAF	Uncertain	0.021	T
BayesDel_noAF	Benign	-0.21
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.25	T;T;T
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	.;D;D
M_CAP	Benign	0.034	D
MetaRNN	Uncertain	0.48	T;T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Uncertain	2.4	M;M;.
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-1.6	N;.;N
REVEL	Benign	0.17
Sift	Uncertain	0.0090	D;.;D
Sift4G	Uncertain	0.032	D;D;D
Polyphen		0.88	P;P;P
Vest4		0.57
MutPred		0.53		Loss of loop (P = 0.2237);Loss of loop (P = 0.2237);.;
MVP		0.54
MPC		1.1
ClinPred		0.95	D
GERP RS		4.0
Varity_R		0.88
gMVP		0.36

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: chr17-40968035;