1-156815564-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003975.4(SH2D2A):​c.124-343A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.903 in 609,098 control chromosomes in the GnomAD database, including 250,060 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.86 ( 56527 hom., cov: 31)
Exomes 𝑓: 0.92 ( 193533 hom. )

Consequence

SH2D2A
NM_003975.4 intron

Scores

2

Clinical Significance

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

Conservation

PhyloP100: -1.71
Variant links:
Genes affected
SH2D2A (HGNC:10821): (SH2 domain containing 2A) This gene encodes an adaptor protein thought to function in T-cell signal transduction. A related protein in mouse is responsible for the activation of lymphocyte-specific protein-tyrosine kinase and functions in downstream signaling. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2010]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.86).
BP6
Variant 1-156815564-T-C is Benign according to our data. Variant chr1-156815564-T-C is described in ClinVar as [Benign]. Clinvar id is 667736.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.936 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SH2D2ANM_003975.4 linkuse as main transcriptc.124-343A>G intron_variant ENST00000368199.8 NP_003966.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SH2D2AENST00000368199.8 linkuse as main transcriptc.124-343A>G intron_variant 1 NM_003975.4 ENSP00000357182 P2Q9NP31-1
SH2D2AENST00000368198.7 linkuse as main transcriptc.70-343A>G intron_variant 1 ENSP00000357181 A2Q9NP31-4
SH2D2AENST00000392306.2 linkuse as main transcriptc.124-343A>G intron_variant 1 ENSP00000376123 Q9NP31-2
SH2D2AENST00000495306.1 linkuse as main transcriptn.176-343A>G intron_variant, non_coding_transcript_variant 5

Frequencies

GnomAD3 genomes
AF:
0.855
AC:
129925
AN:
151934
Hom.:
56484
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.678
Gnomad AMI
AF:
0.971
Gnomad AMR
AF:
0.862
Gnomad ASJ
AF:
0.881
Gnomad EAS
AF:
0.936
Gnomad SAS
AF:
0.896
Gnomad FIN
AF:
0.898
Gnomad MID
AF:
0.905
Gnomad NFE
AF:
0.942
Gnomad OTH
AF:
0.872
GnomAD4 exome
AF:
0.919
AC:
419804
AN:
457048
Hom.:
193533
Cov.:
3
AF XY:
0.919
AC XY:
221626
AN XY:
241210
show subpopulations
Gnomad4 AFR exome
AF:
0.682
Gnomad4 AMR exome
AF:
0.829
Gnomad4 ASJ exome
AF:
0.880
Gnomad4 EAS exome
AF:
0.947
Gnomad4 SAS exome
AF:
0.899
Gnomad4 FIN exome
AF:
0.905
Gnomad4 NFE exome
AF:
0.942
Gnomad4 OTH exome
AF:
0.908
GnomAD4 genome
AF:
0.855
AC:
130024
AN:
152050
Hom.:
56527
Cov.:
31
AF XY:
0.856
AC XY:
63640
AN XY:
74332
show subpopulations
Gnomad4 AFR
AF:
0.679
Gnomad4 AMR
AF:
0.863
Gnomad4 ASJ
AF:
0.881
Gnomad4 EAS
AF:
0.936
Gnomad4 SAS
AF:
0.897
Gnomad4 FIN
AF:
0.898
Gnomad4 NFE
AF:
0.942
Gnomad4 OTH
AF:
0.872
Alfa
AF:
0.913
Hom.:
64431
Bravo
AF:
0.843
Asia WGS
AF:
0.893
AC:
3106
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingGeneDxJun 14, 2018This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.86
CADD
Benign
0.041
DANN
Benign
0.34

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.060
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: rs2150906; hg19: chr1-156785356; COSMIC: COSV63885550; COSMIC: COSV63885550; API