chr8-55941947-A-G
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Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 1P and 8B. PP2BP4_StrongBS2
The NM_002350.4(LYN):c.88A>G(p.Thr30Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0000254 in 1,613,416 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Genomes: 𝑓 0.000092 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000018 ( 0 hom. )
Consequence
LYN
NM_002350.4 missense
NM_002350.4 missense
Scores
2
17
Clinical Significance
Conservation
PhyloP100: 4.39
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -7 ACMG points.
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=0.03427717).
BS2
High AC in GnomAd4 at 14 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LYN | NM_002350.4 | c.88A>G | p.Thr30Ala | missense_variant | 2/13 | ENST00000519728.6 | |
LYN | NM_001111097.3 | c.69+19A>G | intron_variant | ||||
LYN | XM_011517529.4 | c.-135-4501A>G | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LYN | ENST00000519728.6 | c.88A>G | p.Thr30Ala | missense_variant | 2/13 | 1 | NM_002350.4 | P4 | |
LYN | ENST00000520220.6 | c.69+19A>G | intron_variant | 1 | A1 | ||||
LYN | ENST00000520050.1 | c.88A>G | p.Thr30Ala | missense_variant | 2/6 | 4 |
Frequencies
GnomAD3 genomes AF: 0.0000920 AC: 14AN: 152180Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251202Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135798
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GnomAD4 exome AF: 0.0000185 AC: 27AN: 1461236Hom.: 0 Cov.: 30 AF XY: 0.0000110 AC XY: 8AN XY: 726958
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GnomAD4 genome AF: 0.0000920 AC: 14AN: 152180Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1AN XY: 74340
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 17, 2022 | The c.88A>G (p.T30A) alteration is located in exon 2 (coding exon 1) of the LYN gene. This alteration results from a A to G substitution at nucleotide position 88, causing the threonine (T) at amino acid position 30 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Nov 18, 2023 | This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 30 of the LYN protein (p.Thr30Ala). This variant is present in population databases (rs377153434, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with LYN-related conditions. ClinVar contains an entry for this variant (Variation ID: 1504325). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. In 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. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
B;.
Vest4
MVP
MPC
ClinPred
T
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at