Genetic Variant HSH2D:p.Asp103Asp (chr19-16153136-C-T) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001382417.1(HSH2D):c.309C>T(p.Asp103Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00356 in 1,591,756 control chromosomes in the GnomAD database, including 165 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.019 ( 88 hom., cov: 32)

Exomes 𝑓: 0.0020 ( 77 hom. )

Consequence

HSH2D
NM_001382417.1 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.94

Variant links:

Genes affected

HSH2D (HGNC:24920): (hematopoietic SH2 domain containing) T-cell activation requires 2 signals: recognition of antigen by the T-cell receptor (see TCR; MIM 186880) and a costimulatory signal provided primarily by CD28 (MIM 186760) in naive T cells. HSH2 is a target of both of these signaling pathways (Greene et al., 2003 [PubMed 12960172]).[supplied by OMIM, Mar 2008]

HSH2D links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 19-16153136-C-T is Benign according to our data. Variant chr19-16153136-C-T is described in ClinVar as [Benign]. Clinvar id is 777451.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.94 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0628 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSH2D	NM_001382417.1 link	c.309C>T	p.Asp103Asp	synonymous_variant	Exon 4 of 6	ENST00000613986.4	NP_001369346.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HSH2D	ENST00000613986.4 link	c.309C>T	p.Asp103Asp	synonymous_variant	Exon 4 of 6	2	NM_001382417.1	ENSP00000483354.1		Q96JZ2-1

Frequencies

GnomAD3 genomes

AF:

0.0185

AC:

2818

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0646

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00602

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000265

Gnomad OTH

AF:

0.0129

GnomAD3 exomes

AF:

0.00453

AC:

952

AN:

210084

Hom.:

AF XY:

0.00369

AC XY:

419

AN XY:

113696

show subpopulations

Gnomad AFR exome

AF:

0.0664

Gnomad AMR exome

AF:

0.00349

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000132

Gnomad SAS exome

AF:

0.0000376

Gnomad FIN exome

AF:

0.000262

Gnomad NFE exome

AF:

0.000258

Gnomad OTH exome

AF:

0.00169

GnomAD4 exome

AF:

0.00196

AC:

2826

AN:

1439420

Hom.:

Cov.:

AF XY:

0.00176

AC XY:

1256

AN XY:

714136

show subpopulations

Gnomad4 AFR exome

AF:

0.0628

Gnomad4 AMR exome

AF:

0.00392

Gnomad4 ASJ exome

AF:

0.0000389

Gnomad4 EAS exome

AF:

0.0000516

Gnomad4 SAS exome

AF:

0.0000963

Gnomad4 FIN exome

AF:

0.000271

Gnomad4 NFE exome

AF:

0.000263

Gnomad4 OTH exome

AF:

0.00423

GnomAD4 genome

AF:

0.0186

AC:

2835

AN:

152336

Hom.:

Cov.:

AF XY:

0.0178

AC XY:

1329

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.0648

Gnomad4 AMR

AF:

0.00601

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.000265

Gnomad4 OTH

AF:

0.0128

Alfa

AF:

0.00949

Hom.:

Bravo

AF:

0.0208

Asia WGS

AF:

0.00375

AC:

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

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.36

DANN

Benign

0.48

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over