chr19-38915624-G-GCCAGGCAGC

Position:

• chr19-38915624-G-GCCAGGCAGC

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 2P and 16B. PM4 BP6_Very_Strong BS1 BS2

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts U:1 B:5
• Conservation: PhyloP100: -0.230

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]

ENSG00000269547 (HGNC:):

ACMG classification

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/exons	MANE	Protein	UniProt
SARS2	NM_017827.4	c.1530_1538dupGCTGCCTGG	p.Gly513_Gln514insLeuProGly	disruptive_inframe_insertion	16/16	ENST00000221431.11	NP_060297.1
SARS2	NM_001145901.2	c.1536_1544dupGCTGCCTGG	p.Gly515_Gln516insLeuProGly	disruptive_inframe_insertion	17/17		NP_001139373.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SARS2	ENST00000221431.11	c.1530_1538dupGCTGCCTGG	p.Gly513_Gln514insLeuProGly	disruptive_inframe_insertion	16/16	1	NM_017827.4	ENSP00000221431.6
ENSG00000269547	ENST00000599996.1	c.1737_1745dupGCTGCCTGG	p.Gly582_Gln583insLeuProGly	disruptive_inframe_insertion	20/20	2		ENSP00000472465.1

Frequencies

GnomAD3 genomes AF: 0.00153 AC: 233 AN: 152178 Hom.: 0 Cov.: 32

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.: 7 AF XY: 0.00279 AC XY: 378 AN XY: 135342

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.: 17 Cov.: 33 AF XY: 0.00240 AC XY: 1745 AN XY: 726408

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.: 0 Cov.: 32 AF XY: 0.00185 AC XY: 138 AN XY: 74462

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.: 1

Bravo AF: 0.00143

Asia WGS AF: 0.00231 AC: 8 AN: 3478

EpiCase AF: 0.00316

EpiControl AF: 0.00338

ClinVar

Significance: Benign

Submissions summary: Uncertain:1 Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Uncertain:1 Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 22, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 22, 2024	- -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Uncertain significance, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Mar 02, 2016	- -

not specified Benign:1

Benign, no assertion criteria provided

clinical testing

Genome Diagnostics Laboratory, University Medical Center Utrecht

-

- -

SARS2-related disorder Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 20, 2019

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

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs551671819; hg19: chr19-39406264;