13-50910072-GCGGCATGG-ACC

Variant names:

• chr13-50910072-GCGGCATGG-ACC
• NM_024570.4:c.-5_4delGCGGCATGGinsACC

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PVS1_Moderate PM2 PP5_Moderate

The NM_024570.4(RNASEH2B):​c.-5_4delGCGGCATGGinsACC​(p.Met1_Ala2delinsThr???) variant causes a start lost, conservative inframe deletion, synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RNASEH2B NM_024570.4 start_lost, conservative_inframe_deletion, synonymous
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 2.38

Genes affected

RNASEH2B (HGNC:25671): (ribonuclease H2 subunit B) RNase H2 is composed of a single catalytic subunit (A) and two non-catalytic subunits (B and C) and specifically degrades the RNA of RNA:DNA hybrids. The protein encoded by this gene is the non-catalytic B subunit of RNase H2, which is thought to play a role in DNA replication. Multiple transcript variants encoding different isoforms have been found for this gene. Defects in this gene are a cause of Aicardi-Goutieres syndrome type 2 (AGS2). [provided by RefSeq, Nov 2008]

RNASEH2B-AS1 (HGNC:39967): (RNASEH2B antisense RNA 1)

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PVS1: Start lost variant, next in-frame start position is after 1 pathogenic variants. Next in-frame start position is after 90 CDS bases. Genomic position: 50927432. Lost 0.096 part of the original CDS.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 13-50910072-GCGGCATGG-ACC is Pathogenic according to our data. Variant chr13-50910072-GCGGCATGG-ACC is described in ClinVar as [Likely_pathogenic]. Clinvar id is 3576266.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNASEH2B	NM_024570.4	c.-5_4delGCGGCATGGinsACC	p.Met1_Ala2delinsThr???	start_lost, conservative_inframe_deletion, synonymous_variant	Exon 1 of 11	ENST00000336617.8	NP_078846.2
RNASEH2B	NM_024570.4	c.-5_4delGCGGCATGGinsACC		5_prime_UTR_variant	Exon 1 of 11	ENST00000336617.8	NP_078846.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNASEH2B	ENST00000336617.8	c.-5_4delGCGGCATGGinsACC	p.Met1_Ala2delinsThr???	start_lost, conservative_inframe_deletion, synonymous_variant	Exon 1 of 11	1	NM_024570.4	ENSP00000337623.2
RNASEH2B	ENST00000336617	c.-5_4delGCGGCATGGinsACC		5_prime_UTR_variant	Exon 1 of 11	1	NM_024570.4	ENSP00000337623.2

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

Aicardi-Goutieres syndrome 2 Pathogenic:1

Feb 07, 2024

Fulgent Genetics, Fulgent Genetics

Significance: Likely pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr13-51484208;