6-111661835-G-C

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_002037.5(FYN):c.1518C>G(p.Asp506Glu) variant causes a missense change. The variant allele was found at a frequency of 0.0135 in 1,614,168 control chromosomes in the GnomAD database, including 172 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.0092 ( 6 hom., cov: 32)

Exomes 𝑓: 0.014 ( 166 hom. )

Consequence

FYN
NM_002037.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 4.78

Variant links:

Genes affected

FYN (HGNC:4037): (FYN proto-oncogene, Src family tyrosine kinase) This gene is a member of the protein-tyrosine kinase oncogene family. It encodes a membrane-associated tyrosine kinase that has been implicated in the control of cell growth. The protein associates with the p85 subunit of phosphatidylinositol 3-kinase and interacts with the fyn-binding protein. Alternatively spliced transcript variants encoding distinct isoforms exist. [provided by RefSeq, Jul 2008]

FYN links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008390069).

BP6

Variant 6-111661835-G-C is Benign according to our data. Variant chr6-111661835-G-C is described in ClinVar as [Benign]. Clinvar id is 789183.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4_exome allele frequency = 0.0139 (20391/1461868) while in subpopulation NFE AF= 0.0161 (17916/1111992). AF 95% confidence interval is 0.0159. There are 166 homozygotes in gnomad4_exome. There are 10030 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1398 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FYN	NM_002037.5 link	c.1518C>G	p.Asp506Glu	missense_variant	Exon 14 of 14	ENST00000354650.7	NP_002028.1	P06241-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FYN	ENST00000354650.7 link	c.1518C>G	p.Asp506Glu	missense_variant	Exon 14 of 14	1	NM_002037.5	ENSP00000346671.3		P06241-1

Frequencies

GnomAD3 genomes

AF:

0.00918

AC:

1397

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00331

Gnomad AMI

AF:

0.00220

Gnomad AMR

AF:

0.0103

Gnomad ASJ

AF:

0.00490

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00807

Gnomad FIN

AF:

0.00179

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0148

Gnomad OTH

AF:

0.00716

GnomAD3 exomes

AF:

0.00913

AC:

2296

AN:

251466

Hom.:

AF XY:

0.00943

AC XY:

1282

AN XY:

135914

show subpopulations

Gnomad AFR exome

AF:

0.00271

Gnomad AMR exome

AF:

0.00743

Gnomad ASJ exome

AF:

0.00278

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0123

Gnomad FIN exome

AF:

0.00180

Gnomad NFE exome

AF:

0.0130

Gnomad OTH exome

AF:

0.0121

GnomAD4 exome

AF:

0.0139

AC:

20391

AN:

1461868

Hom.:

166

Cov.:

AF XY:

0.0138

AC XY:

10030

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.00284

Gnomad4 AMR exome

AF:

0.00762

Gnomad4 ASJ exome

AF:

0.00363

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.0124

Gnomad4 FIN exome

AF:

0.00208

Gnomad4 NFE exome

AF:

0.0161

Gnomad4 OTH exome

AF:

0.0121

GnomAD4 genome

AF:

0.00918

AC:

1398

AN:

152300

Hom.:

Cov.:

AF XY:

0.00830

AC XY:

618

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.00330

Gnomad4 AMR

AF:

0.0103

Gnomad4 ASJ

AF:

0.00490

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00829

Gnomad4 FIN

AF:

0.00179

Gnomad4 NFE

AF:

0.0148

Gnomad4 OTH

AF:

0.00709

Alfa

AF:

0.0110

Hom.:

Bravo

AF:

0.00963

TwinsUK

AF:

0.0178

AC:

ALSPAC

AF:

0.0205

AC:

ESP6500AA

AF:

0.00295

AC:

ESP6500EA

AF:

0.0170

AC:

146

ExAC

AF:

0.00906

AC:

1100

Asia WGS

AF:

0.00289

AC:

AN:

3478

EpiCase

AF:

0.0149

EpiControl

AF:

0.0142

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Oct 22, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Nov 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

FYN: PP2, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Uncertain

0.61

.;.;D;.;D;.

Eigen

Benign

-0.18

Eigen_PC

Benign

0.023

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.80

T;.;.;T;T;.

MetaRNN

Benign

0.0084

T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.63

.;.;N;.;N;.

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-0.93

N;N;N;N;N;N

REVEL

Benign

0.090

Sift

Benign

0.30

T;T;T;T;T;T

Sift4G

Benign

0.70

T;T;T;T;T;T

Polyphen

0.0010, 0.0

.;.;B;B;B;.

Vest4

0.33

MutPred

0.13

.;.;Gain of glycosylation at P507 (P = 0.0676);.;Gain of glycosylation at P507 (P = 0.0676);.;

MVP

0.48

MPC

1.1

ClinPred

0.0065

GERP RS

4.8

Varity_R

0.38

gMVP

0.67

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over