8-56166548-GGGAGAGGT-G

Position:

• chr8-56166548-GGGAGAGGT-G

Variant summary

Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1_Strong PM2 PP5_Moderate

The NM_002655.3(PLAG1):​c.1190_1197del​(p.Asp397AlafsTer10) variant causes a frameshift change. 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: PLAG1 NM_002655.3 frameshift
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 5.77

Genes affected

PLAG1 (HGNC:9045): (PLAG1 zinc finger) Pleomorphic adenoma gene 1 encodes a zinc finger protein with 2 putative nuclear localization signals. PLAG1, which is developmentally regulated, has been shown to be consistently rearranged in pleomorphic adenomas of the salivary glands. PLAG1 is activated by the reciprocal chromosomal translocations involving 8q12 in a subset of salivary gland pleomorphic adenomas. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_pathogenic. Variant got 8 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.208 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 8-56166548-GGGAGAGGT-G is Pathogenic according to our data. Variant chr8-56166548-GGGAGAGGT-G is described in ClinVar as [Likely_pathogenic]. Clinvar id is 1172638.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLAG1	NM_002655.3	c.1190_1197del	p.Asp397AlafsTer10	frameshift_variant	5/5	ENST00000316981.8	NP_002646.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLAG1	ENST00000316981.8	c.1190_1197del	p.Asp397AlafsTer10	frameshift_variant	5/5	1	NM_002655.3	ENSP00000325546	P1
PLAG1	ENST00000429357.2	c.1190_1197del	p.Asp397AlafsTer10	frameshift_variant	4/4	1		ENSP00000416537	P1
PLAG1	ENST00000522009.1	n.1641_1648del		non_coding_transcript_exon_variant	3/3	1
PLAG1	ENST00000423799.6	c.944_951del	p.Asp315AlafsTer10	frameshift_variant	3/3	2		ENSP00000404067

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

Intellectual disability Pathogenic:1

Likely pathogenic, criteria provided, single submitter

research

Equipe Genetique des Anomalies du Developpement, Université de Bourgogne

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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: chr8-57079107;