dbSNP rs2235708: MCF2:p.Asp823Asp (chrX-139596585-G-A) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001171876.2(MCF2):c.2469C>T(p.Asp823Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0213 in 1,208,139 control chromosomes in the GnomAD database, including 499 homozygotes. There are 8,169 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.041 ( 116 hom., 1300 hem., cov: 23)

Exomes 𝑓: 0.019 ( 383 hom. 6869 hem. )

Consequence

MCF2
NM_001171876.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.153

Publications

2 publications found

Variant links:

Genes affected

MCF2 (HGNC:6940): (MCF.2 cell line derived transforming sequence) The oncogenic protein encoded by this gene is a guanine nucleotide exchange factor (GEF) that exerts control over some members of the Rho family of small GTPases. Several transcript variants encoding different isoforms have been found for this gene. These isoforms exhibit different expression patterns and varying levels of GEF activity.[provided by RefSeq, Jan 2010]

MCF2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant X-139596585-G-A is Benign according to our data. Variant chrX-139596585-G-A is described in ClinVar as Benign. ClinVar VariationId is 1294008.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.153 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0847 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MCF2	NM_001171876.2 link	c.2469C>T	p.Asp823Asp	synonymous_variant	Exon 23 of 29	ENST00000519895.6	NP_001165347.1	P10911-5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MCF2	ENST00000519895.6 link	c.2469C>T	p.Asp823Asp	synonymous_variant	Exon 23 of 29	2	NM_001171876.2	ENSP00000430276.1		P10911-5

Frequencies

GnomAD3 genomes

AF:

0.0408

AC:

4555

AN:

111641

Hom.:

116

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0873

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0600

Gnomad ASJ

AF:

0.00605

Gnomad EAS

AF:

0.0817

Gnomad SAS

AF:

0.0274

Gnomad FIN

AF:

0.0206

Gnomad MID

AF:

0.0335

Gnomad NFE

AF:

0.0126

Gnomad OTH

AF:

0.0411

GnomAD2 exomes

AF:

0.0336

AC:

6151

AN:

182886

AF XY:

0.0298

show subpopulations

Gnomad AFR exome

AF:

0.0913

Gnomad AMR exome

AF:

0.0615

Gnomad ASJ exome

AF:

0.00401

Gnomad EAS exome

AF:

0.0857

Gnomad FIN exome

AF:

0.0208

Gnomad NFE exome

AF:

0.0125

Gnomad OTH exome

AF:

0.0251

GnomAD4 exome

AF:

0.0193

AC:

21211

AN:

1096445

Hom.:

383

Cov.:

AF XY:

0.0190

AC XY:

6869

AN XY:

362149

show subpopulations

African (AFR)

AF:

0.0904

AC:

2382

AN:

26354

American (AMR)

AF:

0.0649

AC:

2280

AN:

35106

Ashkenazi Jewish (ASJ)

AF:

0.00501

AC:

AN:

19355

East Asian (EAS)

AF:

0.116

AC:

3490

AN:

30170

South Asian (SAS)

AF:

0.0309

AC:

1669

AN:

54091

European-Finnish (FIN)

AF:

0.0220

AC:

892

AN:

40494

Middle Eastern (MID)

AF:

0.0167

AC:

AN:

4126

European-Non Finnish (NFE)

AF:

0.0110

AC:

9246

AN:

840723

Other (OTH)

AF:

0.0236

AC:

1086

AN:

46026

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

760

1520

2279

3039

3799

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

450

900

1350

1800

2250

<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:

0.0408

AC:

4559

AN:

111694

Hom.:

116

Cov.:

AF XY:

0.0383

AC XY:

1300

AN XY:

33956

show subpopulations

African (AFR)

AF:

0.0874

AC:

2690

AN:

30764

American (AMR)

AF:

0.0599

AC:

629

AN:

10509

Ashkenazi Jewish (ASJ)

AF:

0.00605

AC:

AN:

2645

East Asian (EAS)

AF:

0.0820

AC:

289

AN:

3526

South Asian (SAS)

AF:

0.0271

AC:

AN:

2689

European-Finnish (FIN)

AF:

0.0206

AC:

126

AN:

6112

Middle Eastern (MID)

AF:

0.0275

AC:

AN:

218

European-Non Finnish (NFE)

AF:

0.0126

AC:

670

AN:

53042

Other (OTH)

AF:

0.0399

AC:

AN:

1502

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

156

312

467

623

779

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

150

200

250

<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:

0.0251

Hom.:

413

Bravo

AF:

0.0474

EpiCase

AF:

0.0122

EpiControl

AF:

0.0106

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jun 13, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.18

(source)

DANN

Benign

0.88

PhyloP100

-0.15

Mutation Taster

=95/5

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over