chr2-85435077-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001394463.1(SH2D6):​c.602C>A​(p.Ser201*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000242 in 1,239,398 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 30)
Exomes 𝑓: 0.0000024 ( 0 hom. )

Consequence

SH2D6
NM_001394463.1 stop_gained

Scores

7

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0430
Variant links:
Genes affected
SH2D6 (HGNC:30439): (SH2 domain containing 6) Predicted to be involved in intracellular signal transduction and transmembrane receptor protein tyrosine kinase signaling pathway. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SH2D6NM_001394463.1 linkc.602C>A p.Ser201* stop_gained Exon 20 of 24 ENST00000469800.7 NP_001381392.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SH2D6ENST00000469800.7 linkc.602C>A p.Ser201* stop_gained Exon 20 of 24 3 NM_001394463.1 ENSP00000510308.1 A0A8I5KXG6

Frequencies

GnomAD3 genomes
Cov.:
30
GnomAD3 exomes
AF:
0.00000408
AC:
1
AN:
245172
Hom.:
0
AF XY:
0.00000750
AC XY:
1
AN XY:
133298
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:
0.00000916
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000242
AC:
3
AN:
1239398
Hom.:
0
Cov.:
37
AF XY:
0.00000489
AC XY:
3
AN XY:
614014
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:
0.00000206
Gnomad4 OTH exome
AF:
0.0000218
GnomAD4 genome
Cov.:
30
ExAC
AF:
0.00000824
AC:
1
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.0094
T
BayesDel_noAF
Benign
-0.25
CADD
Pathogenic
34
DANN
Benign
0.92
Eigen
Benign
-0.37
Eigen_PC
Benign
-0.77
FATHMM_MKL
Benign
0.022
N
Vest4
0.029
GERP RS
-1.4

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.31
Details are displayed if max score is > 0.2
DS_DL_spliceai
0.31
Position offset: 46

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: rs752478609; hg19: chr2-85662200; API