19-38915624-G-GCCAGGCAGC

Variant names:

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 2P and 16B. PM4BP6_Very_StrongBS1BS2

The NM_017827.4(SARS2):c.1530_1538dupGCTGCCTGG(p.Gly513_Gln514insLeuProGly) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00225 in 1,612,656 control chromosomes in the GnomAD database, including 17 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0015 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0023 ( 17 hom. )

Consequence

SARS2
NM_017827.4 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts U:1B:5

Conservation

PhyloP100: -0.230

Variant links:

Genes affected

SARS2 (HGNC:17697): (seryl-tRNA synthetase 2, mitochondrial) This gene encodes the mitochondrial seryl-tRNA synthethase precursor, a member of the class II tRNA synthetase family. The mature enzyme catalyzes the ligation of Serine to tRNA(Ser) and participates in the biosynthesis of selenocysteinyl-tRNA(sec) in mitochondria. The enzyme contains an N-terminal tRNA binding domain and a core catalytic domain. It functions in a homodimeric form, which is stabilized by tRNA binding. This gene is regulated by a bidirectional promoter that also controls the expression of mitochondrial ribosomal protein S12. Both genes are within the critical interval for the autosomal dominant deafness locus DFNA4 and might be linked to this disease. Multiple transcript variants encoding different isoforms have been identified for this gene. [provided by RefSeq, Mar 2009]

SARS2 links:

ENSG00000269547 (HGNC:):

ENSG00000269547 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_017827.4.

BP6

Variant 19-38915624-G-GCCAGGCAGC is Benign according to our data. Variant chr19-38915624-G-GCCAGGCAGC is described in ClinVar as [Benign]. Clinvar id is 215115.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00154 (235/152296) while in subpopulation SAS AF= 0.00705 (34/4822). AF 95% confidence interval is 0.00519. There are 0 homozygotes in gnomad4. There are 138 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 17 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SARS2	NM_017827.4 link	c.1530_1538dupGCTGCCTGG	p.Gly513_Gln514insLeuProGly	disruptive_inframe_insertion	Exon 16 of 16	ENST00000221431.11	NP_060297.1	Q9NP81-1
SARS2	NM_001145901.2 link	c.1536_1544dupGCTGCCTGG	p.Gly515_Gln516insLeuProGly	disruptive_inframe_insertion	Exon 17 of 17		NP_001139373.1	Q9NP81-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SARS2	ENST00000221431.11 link	c.1530_1538dupGCTGCCTGG	p.Gly513_Gln514insLeuProGly	disruptive_inframe_insertion	Exon 16 of 16	1	NM_017827.4	ENSP00000221431.6		Q9NP81-1
ENSG00000269547	ENST00000599996.1 link	c.1737_1745dupGCTGCCTGG	p.Gly582_Gln583insLeuProGly	disruptive_inframe_insertion	Exon 20 of 20	2		ENSP00000472465.1		M0R2C6

Frequencies

GnomAD3 genomes

AF:

0.00153

AC:

233

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000851

Gnomad ASJ

AF:

0.00230

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00663

Gnomad FIN

AF:

0.00254

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00216

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00248

AC:

621

AN:

250394

Hom.:

AF XY:

0.00279

AC XY:

378

AN XY:

135342

show subpopulations

Gnomad AFR exome

AF:

0.000309

Gnomad AMR exome

AF:

0.00122

Gnomad ASJ exome

AF:

0.00169

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00779

Gnomad FIN exome

AF:

0.00240

Gnomad NFE exome

AF:

0.00221

Gnomad OTH exome

AF:

0.00295

GnomAD4 exome

AF:

0.00232

AC:

3394

AN:

1460360

Hom.:

Cov.:

AF XY:

0.00240

AC XY:

1745

AN XY:

726408

show subpopulations

Gnomad4 AFR exome

AF:

0.000419

Gnomad4 AMR exome

AF:

0.00125

Gnomad4 ASJ exome

AF:

0.00161

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00773

Gnomad4 FIN exome

AF:

0.00211

Gnomad4 NFE exome

AF:

0.00208

Gnomad4 OTH exome

AF:

0.00259

GnomAD4 genome

AF:

0.00154

AC:

235

AN:

152296

Hom.:

Cov.:

AF XY:

0.00185

AC XY:

138

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.0000962

Gnomad4 AMR

AF:

0.000850

Gnomad4 ASJ

AF:

0.00230

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00705

Gnomad4 FIN

AF:

0.00254

Gnomad4 NFE

AF:

0.00216

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00213

Hom.:

Bravo

AF:

0.00143

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.00316

EpiControl

AF:

0.00338

ClinVar

Significance: Benign

Submissions summary: Uncertain:1Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:3

Feb 22, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Mar 02, 2016

Mayo Clinic Laboratories, Mayo Clinic

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

SARS2-related disorder

Benign:1

Feb 20, 2019

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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