3-183207639-G-A

Variant summary

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

The NM_015078.4(MCF2L2):c.2681C>T(p.Ser894Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,792 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: MCF2L2 NM_015078.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.71

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=0.23295715).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MCF2L2	NM_015078.4	c.2681C>T	p.Ser894Phe	missense_variant	23/30	ENST00000328913.8
MCF2L2	XM_017005943.3	c.2681C>T	p.Ser894Phe	missense_variant	23/26
MCF2L2	XM_011512585.3	c.1622C>T	p.Ser541Phe	missense_variant	15/22
MCF2L2	XM_047447751.1	c.1580C>T	p.Ser527Phe	missense_variant	14/21

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MCF2L2	ENST00000328913.8	c.2681C>T	p.Ser894Phe	missense_variant	23/30	5	NM_015078.4	A2
MCF2L2	ENST00000473233.5	c.2681C>T	p.Ser894Phe	missense_variant	23/29	5		P4
MCF2L2	ENST00000468976.5	n.62C>T		non_coding_transcript_exon_variant	1/6	4
MCF2L2	ENST00000488149.5	n.7128C>T		non_coding_transcript_exon_variant	24/28	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461792 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 727200

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

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 27, 2024

The c.2681C>T (p.S894F) alteration is located in exon 23 (coding exon 23) of the MCF2L2 gene. This alteration results from a C to T substitution at nucleotide position 2681, causing the serine (S) at amino acid position 894 to be replaced by a phenylalanine (F). 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	0.091
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
Cadd	Benign	21
Dann	Uncertain	1.0
DEOGEN2	Benign	0.033	T;.
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.26
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.63	T;T
M_CAP	Benign	0.0089	T
MetaRNN	Benign	0.23	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M;M
MutationTaster	Benign	0.83	D;D
PrimateAI	Benign	0.35	T
PROVEAN	Uncertain	-3.1	D;D
REVEL	Benign	0.12
Sift	Uncertain	0.018	D;D
Sift4G	Uncertain	0.0030	D;D
Polyphen		0.72	P;.
Vest4		0.33
MutPred		0.52		Loss of disorder (P = 0.0138);Loss of disorder (P = 0.0138);
MVP		0.28
MPC		0.51
ClinPred		0.97	D
GERP RS		2.9
Varity_R		0.10
gMVP		0.19

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: chr3-182925427;