dbSNP rs7639705: MCF2L2:p.Ile359Leu (chr3-183309754-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_015078.4(MCF2L2):c.1075A>C(p.Ile359Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.223 in 1,613,322 control chromosomes in the GnomAD database, including 43,514 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.27 ( 6290 hom., cov: 30)

Exomes 𝑓: 0.22 ( 37224 hom. )

Consequence

MCF2L2
NM_015078.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.68

Publications

25 publications found

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]

MCF2L2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006294757).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.391 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MCF2L2	NM_015078.4 link	c.1075A>C	p.Ile359Leu	missense_variant	Exon 10 of 30	ENST00000328913.8	NP_055893.4	Q86YR7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MCF2L2	ENST00000328913.8 link	c.1075A>C	p.Ile359Leu	missense_variant	Exon 10 of 30	5	NM_015078.4	ENSP00000328118.3		Q86YR7-1

Frequencies

GnomAD3 genomes

AF:

0.273

AC:

41315

AN:

151452

Hom.:

6273

Cov.:

show subpopulations

Gnomad AFR

AF:

0.396

Gnomad AMI

AF:

0.302

Gnomad AMR

AF:

0.272

Gnomad ASJ

AF:

0.230

Gnomad EAS

AF:

0.363

Gnomad SAS

AF:

0.325

Gnomad FIN

AF:

0.255

Gnomad MID

AF:

0.225

Gnomad NFE

AF:

0.194

Gnomad OTH

AF:

0.236

GnomAD2 exomes

AF:

0.257

AC:

64609

AN:

251424

AF XY:

0.253

show subpopulations

Gnomad AFR exome

AF:

0.402

Gnomad AMR exome

AF:

0.286

Gnomad ASJ exome

AF:

0.235

Gnomad EAS exome

AF:

0.371

Gnomad FIN exome

AF:

0.254

Gnomad NFE exome

AF:

0.194

Gnomad OTH exome

AF:

0.237

GnomAD4 exome

AF:

0.218

AC:

318965

AN:

1461752

Hom.:

37224

Cov.:

AF XY:

0.220

AC XY:

159661

AN XY:

727192

show subpopulations

African (AFR)

AF:

0.407

AC:

13608

AN:

33474

American (AMR)

AF:

0.282

AC:

12621

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.231

AC:

6049

AN:

26136

East Asian (EAS)

AF:

0.365

AC:

14485

AN:

39700

South Asian (SAS)

AF:

0.316

AC:

27278

AN:

86254

European-Finnish (FIN)

AF:

0.248

AC:

13255

AN:

53414

Middle Eastern (MID)

AF:

0.212

AC:

1221

AN:

5768

European-Non Finnish (NFE)

AF:

0.195

AC:

216381

AN:

1111906

Other (OTH)

AF:

0.233

AC:

14067

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

12925

25850

38776

51701

64626

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7874

15748

23622

31496

39370

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.273

AC:

41382

AN:

151570

Hom.:

6290

Cov.:

AF XY:

0.276

AC XY:

20444

AN XY:

74022

show subpopulations

African (AFR)

AF:

0.396

AC:

16351

AN:

41262

American (AMR)

AF:

0.272

AC:

4139

AN:

15218

Ashkenazi Jewish (ASJ)

AF:

0.230

AC:

796

AN:

3466

East Asian (EAS)

AF:

0.364

AC:

1850

AN:

5088

South Asian (SAS)

AF:

0.325

AC:

1561

AN:

4800

European-Finnish (FIN)

AF:

0.255

AC:

2675

AN:

10482

Middle Eastern (MID)

AF:

0.241

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.194

AC:

13163

AN:

67952

Other (OTH)

AF:

0.239

AC:

501

AN:

2098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1422

2844

4265

5687

7109

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

416

832

1248

1664

2080

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.220

Hom.:

14528

Bravo

AF:

0.280

TwinsUK

AF:

0.195

AC:

723

ALSPAC

AF:

0.183

AC:

706

ESP6500AA

AF:

0.400

AC:

1762

ESP6500EA

AF:

0.196

AC:

1689

ExAC

AF:

0.256

AC:

31121

Asia WGS

AF:

0.351

AC:

1221

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.046

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.67

CADD

Benign

(source)

DANN

Benign

0.26

DEOGEN2

Benign

0.0019

T;.;.;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.92

FATHMM_MKL

Benign

0.030

LIST_S2

Benign

0.039

T;T;T;T

MetaRNN

Benign

0.0063

T;T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

-1.7

N;N;N;N

PhyloP100

2.7

PrimateAI

Uncertain

0.53

PROVEAN

Benign

0.77

N;N;N;N

REVEL

Benign

0.099

Sift

Benign

1.0

T;T;T;T

Sift4G

Benign

1.0

T;T;T;T

Polyphen

0.0

B;.;B;.

Vest4

0.091

MPC

0.18

ClinPred

0.0025

GERP RS

3.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.068

gMVP

0.24

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over