rs2038123

Positions:

• chr20-34108259-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003908.5(EIF2S2):​c.16-2714T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0851 in 152,298 control chromosomes in the GnomAD database, including 616 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.085 (616 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: EIF2S2 NM_003908.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.723

Genes affected

EIF2S2 (HGNC:3266): (eukaryotic translation initiation factor 2 subunit beta) Eukaryotic translation initiation factor 2 (EIF-2) functions in the early steps of protein synthesis by forming a ternary complex with GTP and initiator tRNA and binding to a 40S ribosomal subunit. EIF-2 is composed of three subunits, alpha, beta, and gamma, with the protein encoded by this gene representing the beta subunit. The beta subunit catalyzes the exchange of GDP for GTP, which recycles the EIF-2 complex for another round of initiation. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2015]

RALY (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.122 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EIF2S2	NM_003908.5	c.16-2714T>C		intron_variant		ENST00000374980.3	NP_003899.2
EIF2S2	NM_001316363.2	c.16-2714T>C		intron_variant			NP_001303292.1
EIF2S2	NM_001316364.2	c.16-2714T>C		intron_variant			NP_001303293.1
EIF2S2	XM_017028118.2	c.1-2714T>C		intron_variant			XP_016883607.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EIF2S2	ENST00000374980.3	c.16-2714T>C		intron_variant		1	NM_003908.5	ENSP00000364119.2
RALY	ENST00000489384.1	n.178A>G		non_coding_transcript_exon_variant	3/3	3

Frequencies

GnomAD3 genomes AF: 0.0851 AC: 12950 AN: 152180 Hom.: 616 Cov.: 32

Gnomad AFR AF: 0.124

Gnomad AMI AF: 0.0768

Gnomad AMR AF: 0.0539

Gnomad ASJ AF: 0.103

Gnomad EAS AF: 0.0943

Gnomad SAS AF: 0.0988

Gnomad FIN AF: 0.0846

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0658

Gnomad OTH AF: 0.0826

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 6 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 4

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.0851 AC: 12962 AN: 152298 Hom.: 616 Cov.: 32 AF XY: 0.0873 AC XY: 6500 AN XY: 74474

Gnomad4 AFR AF: 0.124

Gnomad4 AMR AF: 0.0537

Gnomad4 ASJ AF: 0.103

Gnomad4 EAS AF: 0.0945

Gnomad4 SAS AF: 0.0995

Gnomad4 FIN AF: 0.0846

Gnomad4 NFE AF: 0.0657

Gnomad4 OTH AF: 0.0822

Alfa AF: 0.0720 Hom.: 595

Bravo AF: 0.0820

Asia WGS AF: 0.0890 AC: 309 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	15
DANN	Benign	0.90

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

Other links and lift over

dbSNP: rs2038123; hg19: chr20-32696065;