chr3-183207739-C-T

Variant summary

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

The NM_015078.4(MCF2L2):​c.2581G>A​(p.Asp861Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000867 in 1,614,048 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

MCF2L2
NM_015078.4 missense

Scores

1
10
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.68
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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/exons MANE UniProt
MCF2L2NM_015078.4 linkuse as main transcriptc.2581G>A p.Asp861Asn missense_variant 23/30 ENST00000328913.8
MCF2L2XM_017005943.3 linkuse as main transcriptc.2581G>A p.Asp861Asn missense_variant 23/26
MCF2L2XM_011512585.3 linkuse as main transcriptc.1522G>A p.Asp508Asn missense_variant 15/22
MCF2L2XM_047447751.1 linkuse as main transcriptc.1480G>A p.Asp494Asn missense_variant 14/21

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MCF2L2ENST00000328913.8 linkuse as main transcriptc.2581G>A p.Asp861Asn missense_variant 23/305 NM_015078.4 A2Q86YR7-1
MCF2L2ENST00000473233.5 linkuse as main transcriptc.2581G>A p.Asp861Asn missense_variant 23/295 P4Q86YR7-4
MCF2L2ENST00000488149.5 linkuse as main transcriptn.7028G>A non_coding_transcript_exon_variant 24/282
MCF2L2ENST00000468976.5 linkuse as main transcript upstream_gene_variant 4

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152178
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000262
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000239
AC:
6
AN:
251290
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135804
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000116
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000880
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.00000684
AC:
10
AN:
1461870
Hom.:
0
Cov.:
33
AF XY:
0.00000550
AC XY:
4
AN XY:
727240
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000157
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:
0.0000166
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152178
Hom.:
0
Cov.:
33
AF XY:
0.0000269
AC XY:
2
AN XY:
74348
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000262
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000282
Hom.:
0
Bravo
AF:
0.0000264
ExAC
AF:
0.0000165
AC:
2

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsNov 08, 2022The c.2581G>A (p.D861N) alteration is located in exon 23 (coding exon 23) of the MCF2L2 gene. This alteration results from a G to A substitution at nucleotide position 2581, causing the aspartic acid (D) at amino acid position 861 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
Benign
0.31
BayesDel_addAF
Benign
-0.40
T
BayesDel_noAF
Benign
-0.59
CADD
Uncertain
25
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.053
T;.
Eigen
Uncertain
0.62
Eigen_PC
Uncertain
0.60
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Uncertain
0.94
D;D
M_CAP
Benign
0.0071
T
MetaRNN
Uncertain
0.49
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.8
M;M
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.50
T
PROVEAN
Uncertain
-3.7
D;D
REVEL
Benign
0.24
Sift
Uncertain
0.0020
D;D
Sift4G
Uncertain
0.0030
D;D
Polyphen
0.99
D;.
Vest4
0.49
MutPred
0.39
Gain of MoRF binding (P = 0.0728);Gain of MoRF binding (P = 0.0728);
MVP
0.51
MPC
0.67
ClinPred
0.93
D
GERP RS
4.8
Varity_R
0.70
gMVP
0.52

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs775017211; hg19: chr3-182925527; API