rs2038123

Variant names:

• chr20-34108259-A-G
• rs2038123
• NM_003908.5:c.16-2714T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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:15921): (RALY heterogeneous nuclear ribonucleoprotein) This gene encodes a member of the heterogeneous nuclear ribonucleoprotein (hnRNP) gene family. This protein may play a role in pre-mRNA splicing and in embryonic development. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Sep 2011]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
EIF2S2	NM_003908.5	c.16-2714T>C		intron_variant	Intron 1 of 8	ENST00000374980.3	NP_003899.2
EIF2S2	NM_001316363.2	c.16-2714T>C		intron_variant	Intron 1 of 8		NP_001303292.1
EIF2S2	NM_001316364.2	c.16-2714T>C		intron_variant	Intron 1 of 7		NP_001303293.1
EIF2S2	XM_017028118.2	c.1-2714T>C		intron_variant	Intron 1 of 8		XP_016883607.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EIF2S2	ENST00000374980.3	c.16-2714T>C		intron_variant	Intron 1 of 8	1	NM_003908.5	ENSP00000364119.2
RALY	ENST00000489384.1	n.178A>G		non_coding_transcript_exon_variant	Exon 3 of 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

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) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 4

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.124 AC: 5171 AN: 41554

American (AMR) AF: 0.0537 AC: 822 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.103 AC: 359 AN: 3470

East Asian (EAS) AF: 0.0945 AC: 490 AN: 5186

South Asian (SAS) AF: 0.0995 AC: 480 AN: 4824

European-Finnish (FIN) AF: 0.0846 AC: 898 AN: 10616

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0657 AC: 4471 AN: 68018

Other (OTH) AF: 0.0822 AC: 174 AN: 2116

Alfa AF: 0.0726 Hom.: 753

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
PhyloP100		0.72
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: rs2038123; hg19: chr20-32696065;