rs2090256422

Variant names:

• chr20-25407872-G-CA
• rs2090256422
• NM_021067.5:c.52delGinsCA

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_021067.5(GINS1):​c.52delGinsCA​(p.Glu18GlnfsTer24) variant causes a frameshift, missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: GINS1 NM_021067.5 frameshift, missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 4.96
• Publications: 0 publications found

Genes affected

GINS1 (HGNC:28980): (GINS complex subunit 1) The yeast heterotetrameric GINS complex is made up of Sld5 (GINS4; MIM 610611), Psf1, Psf2 (GINS2; MIM 610609), and Psf3 (GINS3; MIM 610610). The formation of the GINS complex is essential for the initiation of DNA replication in yeast and Xenopus egg extracts (Ueno et al., 2005 [PubMed 16287864]).[supplied by OMIM, Mar 2008]

GINS1 Gene-Disease associations (from GenCC):

• combined immunodeficiency due to GINS1 deficiency

  Inheritance: AR, Unknown Classification: SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)

LOC105372581 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021067.5. 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
	GINS1	NM_021067.5	MANE Select	c.52delGinsCA	p.Glu18GlnfsTer24	frameshift missense	Exon 1 of 7	NP_066545.3
	GINS1	NM_001410830.1		c.52delGinsCA	p.Glu18GlnfsTer24	frameshift missense	Exon 1 of 6	NP_001397759.1	A0A8Q3WLL7
	GINS1	NM_001410831.1		c.52delGinsCA	p.Glu18GlnfsTer13	frameshift missense	Exon 1 of 4	NP_001397760.1	A0A8Q3WLJ3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GINS1	ENST00000262460.5	TSL:1 MANE Select	c.52delGinsCA	p.Glu18GlnfsTer24	frameshift missense	Exon 1 of 7	ENSP00000262460.4	Q14691
	GINS1	ENST00000696814.1		c.52delGinsCA	p.Glu18GlnfsTer24	frameshift missense	Exon 1 of 8	ENSP00000512895.1	A0A8Q3WMM5
	GINS1	ENST00000696894.1		c.52delGinsCA	p.Glu18GlnfsTer24	frameshift missense	Exon 1 of 7	ENSP00000512956.1	A0A8Q3SJ10

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	1	-	Combined immunodeficiency due to GINS1 deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		5.0

Splicing

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

Other links and lift over

dbSNP: rs2090256422; hg19: chr20-25388508;