chr19-16153136-C-T

Variant names:

• chr19-16153136-C-T
• rs1870354
• NM_001382417.1:c.309C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.94
• Publications: 1 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001382417.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSH2D	NM_001382417.1	MANE Select	c.309C>T	p.Asp103Asp	synonymous	Exon 4 of 6	NP_001369346.1	Q96JZ2-1
	HSH2D	NM_032855.4		c.309C>T	p.Asp103Asp	synonymous	Exon 6 of 8	NP_116244.1	Q96JZ2-1
	HSH2D	NM_001369808.1		c.234C>T	p.Asp78Asp	synonymous	Exon 4 of 6	NP_001356737.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSH2D	ENST00000613986.4	TSL:2 MANE Select	c.309C>T	p.Asp103Asp	synonymous	Exon 4 of 6	ENSP00000483354.1	Q96JZ2-1
	HSH2D	ENST00000616645.4	TSL:1	c.309C>T	p.Asp103Asp	synonymous	Exon 6 of 8	ENSP00000482604.1	Q96JZ2-1
	HSH2D	ENST00000874628.1		c.309C>T	p.Asp103Asp	synonymous	Exon 4 of 6	ENSP00000544687.1

Frequencies

GnomAD3 genomes AF: 0.0185 AC: 2818 AN: 152218 Hom.: 86 Cov.: 32

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

GnomAD2 exomes AF: 0.00453 AC: 952 AN: 210084 AF XY: 0.00369

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 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.: 77 Cov.: 31 AF XY: 0.00176 AC XY: 1256 AN XY: 714136

African (AFR) AF: 0.0628 AC: 2075 AN: 33060

American (AMR) AF: 0.00392 AC: 160 AN: 40780

Ashkenazi Jewish (ASJ) AF: 0.0000389 AC: 1 AN: 25706

East Asian (EAS) AF: 0.0000516 AC: 2 AN: 38738

South Asian (SAS) AF: 0.0000963 AC: 8 AN: 83064

European-Finnish (FIN) AF: 0.000271 AC: 14 AN: 51754

Middle Eastern (MID) AF: 0.00495 AC: 24 AN: 4850

European-Non Finnish (NFE) AF: 0.000263 AC: 290 AN: 1101956

Other (OTH) AF: 0.00423 AC: 252 AN: 59512

GnomAD4 genome AF: 0.0186 AC: 2835 AN: 152336 Hom.: 88 Cov.: 32 AF XY: 0.0178 AC XY: 1329 AN XY: 74488

African (AFR) AF: 0.0648 AC: 2694 AN: 41576

American (AMR) AF: 0.00601 AC: 92 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.000188 AC: 2 AN: 10626

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000265 AC: 18 AN: 68030

Other (OTH) AF: 0.0128 AC: 27 AN: 2114

Alfa AF: 0.0169 Hom.: 59

Bravo AF: 0.0208

Asia WGS AF: 0.00375 AC: 13 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.36
DANN	Benign	0.48
PhyloP100		-2.9
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1870354; hg19: chr19-16263946;