chr1-156815752-AC-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_003975.4(SH2D2A):​c.123+253del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00392 in 1,551,468 control chromosomes in the GnomAD database, including 212 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.021 ( 121 hom., cov: 32)
Exomes 𝑓: 0.0021 ( 91 hom. )

Consequence

SH2D2A
NM_003975.4 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.01
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]
NTRK1 (HGNC:8031): (neurotrophic receptor tyrosine kinase 1) This gene encodes a member of the neurotrophic tyrosine kinase receptor (NTKR) family. This kinase is a membrane-bound receptor that, upon neurotrophin binding, phosphorylates itself and members of the MAPK pathway. The presence of this kinase leads to cell differentiation and may play a role in specifying sensory neuron subtypes. Mutations in this gene have been associated with congenital insensitivity to pain, anhidrosis, self-mutilating behavior, cognitive disability and cancer. Alternate transcriptional splice variants of this gene have been found, but only three have been characterized to date. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6
Variant 1-156815752-AC-A is Benign according to our data. Variant chr1-156815752-AC-A is described in ClinVar as [Benign]. Clinvar id is 1221990.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0693 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SH2D2ANM_003975.4 linkuse as main transcriptc.123+253del 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.123+253del intron_variant 1 NM_003975.4 ENSP00000357182 P2Q9NP31-1

Frequencies

GnomAD3 genomes
AF:
0.0207
AC:
3145
AN:
152134
Hom.:
121
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0715
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00857
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000414
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.000294
Gnomad OTH
AF:
0.0143
GnomAD4 exome
AF:
0.00210
AC:
2936
AN:
1399216
Hom.:
91
Cov.:
25
AF XY:
0.00177
AC XY:
1236
AN XY:
699920
show subpopulations
Gnomad4 AFR exome
AF:
0.0685
Gnomad4 AMR exome
AF:
0.00455
Gnomad4 ASJ exome
AF:
0.000116
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000165
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000174
Gnomad4 OTH exome
AF:
0.00489
GnomAD4 genome
AF:
0.0207
AC:
3149
AN:
152252
Hom.:
121
Cov.:
32
AF XY:
0.0201
AC XY:
1500
AN XY:
74446
show subpopulations
Gnomad4 AFR
AF:
0.0714
Gnomad4 AMR
AF:
0.00856
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000294
Gnomad4 OTH
AF:
0.0142
Alfa
AF:
0.0153
Hom.:
10
Bravo
AF:
0.0235

ClinVar

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

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxMar 26, 2020- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.090
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: rs146775862; hg19: chr1-156785544; API