rs113477773

Variant names:

• chr16-23522873-T-C
• rs113477773
• NM_001083614.2:c.*1498A>G

Your query was ambiguous. Multiple possible variants found:

• chr16-23522873-T-C
• chr16-23522873-T-G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001083614.2(EARS2):​c.*1498A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0147 in 152,284 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.015 (23 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: EARS2 NM_001083614.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.21
• Publications: 1 publications found

Genes affected

EARS2 (HGNC:29419): (glutamyl-tRNA synthetase 2, mitochondrial) This gene encodes a member of the class I family of aminoacyl-tRNA synthetases. These enzymes play a critical role in protein biosynthesis by charging tRNAs with their cognate amino acids. This protein is encoded by the nuclear genome but is likely to be imported to the mitochondrion where it is thought to catalyze the ligation of glutamate to tRNA molecules. Mutations in this gene have been associated with combined oxidative phosphorylation deficiency 12 (COXPD12). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2015]

GGA2 (HGNC:16064): (golgi associated, gamma adaptin ear containing, ARF binding protein 2) This gene encodes a member of the Golgi-localized, gamma adaptin ear-containing, ARF-binding (GGA) family. This family includes ubiquitous coat proteins that regulate the trafficking of proteins between the trans-Golgi network and the lysosome. These proteins share an amino-terminal VHS domain which mediates sorting of the mannose 6-phosphate receptors at the trans-Golgi network. They also contain a carboxy-terminal region with homology to the ear domain of gamma-adaptins. This family member may play a significant role in cargo molecules regulation and clathrin-coated vesicle assembly. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 16-23522873-T-C is Benign according to our data. Variant chr16-23522873-T-C is described in ClinVar as Benign. ClinVar VariationId is 318517.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0147 (2244/152284) while in subpopulation SAS AF = 0.0199 (96/4828). AF 95% confidence interval is 0.0181. There are 23 homozygotes in GnomAd4. There are 1065 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 23 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001083614.2. 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
	EARS2	NM_001083614.2	MANE Select	c.*1498A>G		3_prime_UTR	Exon 9 of 9	NP_001077083.1	Q5JPH6-1
	EARS2	NR_003501.2		n.2984A>G		non_coding_transcript_exon	Exon 10 of 10

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EARS2	ENST00000449606.7	TSL:1 MANE Select	c.*1498A>G		3_prime_UTR	Exon 9 of 9	ENSP00000395196.2	Q5JPH6-1
	EARS2	ENST00000564987.1	TSL:1	n.2621A>G		non_coding_transcript_exon	Exon 9 of 9
	EARS2	ENST00000674054.1		n.*1405A>G		non_coding_transcript_exon	Exon 10 of 10	ENSP00000501251.1	Q5JPH6-1

Frequencies

GnomAD3 genomes AF: 0.0148 AC: 2249 AN: 152166 Hom.: 24 Cov.: 33

Gnomad AFR AF: 0.0193

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.0128

Gnomad ASJ AF: 0.0207

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0205

Gnomad FIN AF: 0.00188

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0149

Gnomad OTH AF: 0.0148

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 8 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 6

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 8

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.0147 AC: 2244 AN: 152284 Hom.: 23 Cov.: 33 AF XY: 0.0143 AC XY: 1065 AN XY: 74466

African (AFR) AF: 0.0192 AC: 799 AN: 41568

American (AMR) AF: 0.0128 AC: 195 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0207 AC: 72 AN: 3470

East Asian (EAS) AF: 0.00154 AC: 8 AN: 5184

South Asian (SAS) AF: 0.0199 AC: 96 AN: 4828

European-Finnish (FIN) AF: 0.00188 AC: 20 AN: 10622

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0149 AC: 1014 AN: 68012

Other (OTH) AF: 0.0147 AC: 31 AN: 2110

Alfa AF: 0.0172 Hom.: 3

Bravo AF: 0.0158

Asia WGS AF: 0.00549 AC: 19 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Leukoencephalopathy-thalamus and brainstem anomalies-high lactate syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.85
DANN	Benign	0.21
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism

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: rs113477773; hg19: chr16-23534194;