3-183207716-G-T

Position:

• chr3-183207716-G-T

Variant summary

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

The NM_015078.4(MCF2L2):​c.2604C>A​(p.Ser868Arg) 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: MCF2L2 NM_015078.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.97

Genes affected

MCF2L2 (HGNC:30319): (MCF.2 cell line derived transforming sequence-like 2) Predicted to enable guanyl-nucleotide exchange factor activity. Predicted to be involved in regulation of catalytic activity. [provided by Alliance of Genome Resources, Apr 2022]

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=0.2315053).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MCF2L2	NM_015078.4	c.2604C>A	p.Ser868Arg	missense_variant	23/30	ENST00000328913.8
MCF2L2	XM_017005943.3	c.2604C>A	p.Ser868Arg	missense_variant	23/26
MCF2L2	XM_011512585.3	c.1545C>A	p.Ser515Arg	missense_variant	15/22
MCF2L2	XM_047447751.1	c.1503C>A	p.Ser501Arg	missense_variant	14/21

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MCF2L2	ENST00000328913.8	c.2604C>A	p.Ser868Arg	missense_variant	23/30	5	NM_015078.4	A2
MCF2L2	ENST00000473233.5	c.2604C>A	p.Ser868Arg	missense_variant	23/29	5		P4
MCF2L2	ENST00000488149.5	n.7051C>A		non_coding_transcript_exon_variant	24/28	2
MCF2L2	ENST00000468976.5			upstream_gene_variant		4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

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

Feb 28, 2023

The c.2604C>A (p.S868R) alteration is located in exon 23 (coding exon 23) of the MCF2L2 gene. This alteration results from a C to A substitution at nucleotide position 2604, causing the serine (S) at amino acid position 868 to be replaced by an arginine (R). 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	Pathogenic	0.81
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.013	T;.
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.36
FATHMM_MKL	Benign	0.64	D
LIST_S2	Benign	0.81	T;T
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.23	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L;L
MutationTaster	Benign	0.82	N;N
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.74	N;N
REVEL	Benign	0.052
Sift	Benign	0.13	T;D
Sift4G	Benign	0.093	T;T
Polyphen		0.0060	B;.
Vest4		0.27
MutPred		0.70		Gain of MoRF binding (P = 0.0364);Gain of MoRF binding (P = 0.0364);
MVP		0.16
MPC		0.22
ClinPred		0.46	T
GERP RS		1.6
Varity_R		0.11
gMVP		0.53

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: chr3-182925504;