chr8-55941933-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate

The NM_002350.4(LYN):​c.74G>A​(p.Arg25His) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,460,240 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: 31)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

LYN
NM_002350.4 missense

Scores

6
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.30
Variant links:
Genes affected
LYN (HGNC:6735): (LYN proto-oncogene, Src family tyrosine kinase) This gene encodes a tyrosine protein kinase, which maybe involved in the regulation of mast cell degranulation, and erythroid differentiation. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2011]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant in gene, where missense usually causes diseases (based on misZ statistic), LYN. . Gene score misZ 3.3381 (greater than the threshold 3.09). Trascript score misZ 3.9896 (greater than threshold 3.09). GenCC has associacion of gene with autoinflammatory disease, systemic, with vasculitis.
BP4
Computational evidence support a benign effect (MetaRNN=0.24408099).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
LYNNM_002350.4 linkuse as main transcriptc.74G>A p.Arg25His missense_variant 2/13 ENST00000519728.6
LYNNM_001111097.3 linkuse as main transcriptc.69+5G>A splice_donor_5th_base_variant, intron_variant
LYNXM_011517529.4 linkuse as main transcriptc.-135-4515G>A intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
LYNENST00000519728.6 linkuse as main transcriptc.74G>A p.Arg25His missense_variant 2/131 NM_002350.4 P4P07948-1
LYNENST00000520220.6 linkuse as main transcriptc.69+5G>A splice_donor_5th_base_variant, intron_variant 1 A1P07948-2
LYNENST00000520050.1 linkuse as main transcriptc.74G>A p.Arg25His missense_variant 2/64

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251120
Hom.:
0
AF XY:
0.00000737
AC XY:
1
AN XY:
135748
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
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:
0.00
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1460240
Hom.:
0
Cov.:
30
AF XY:
0.00000138
AC XY:
1
AN XY:
726528
show subpopulations
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.:
31

ClinVar

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

Submissions by phenotype

not provided Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingInvitaeMar 13, 2022In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. This variant has not been reported in the literature in individuals affected with LYN-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.0009%). This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 25 of the LYN protein (p.Arg25His). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.18
BayesDel_addAF
Uncertain
0.049
T
BayesDel_noAF
Benign
-0.17
CADD
Pathogenic
28
DANN
Uncertain
1.0
DEOGEN2
Benign
0.33
T;.
Eigen
Uncertain
0.32
Eigen_PC
Uncertain
0.46
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Benign
0.80
T;T
M_CAP
Benign
0.037
D
MetaRNN
Benign
0.24
T;T
MetaSVM
Benign
-0.49
T
MutationAssessor
Benign
1.7
L;.
MutationTaster
Benign
0.99
D;D
PrimateAI
Uncertain
0.50
T
PROVEAN
Benign
-0.66
N;N
REVEL
Benign
0.13
Sift
Benign
0.13
T;T
Sift4G
Benign
0.18
T;T
Polyphen
0.54
P;.
Vest4
0.42
MVP
0.82
MPC
1.2
ClinPred
0.44
T
GERP RS
5.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.065
gMVP
0.47

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: rs1341743995; hg19: chr8-56854492; API