chr6-89862601-A-T

Variant names:

• chr6-89862601-A-T
• NM_001137667.2:c.892A>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001137667.2(CASP8AP2):​c.892A>T​(p.Thr298Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 9/11 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CASP8AP2 NM_001137667.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.298
• Publications: 0 publications found

Genes affected

CASP8AP2 (HGNC:1510): (caspase 8 associated protein 2) This protein is highly similar to FLASH, a mouse apoptotic protein identified by its interaction with the death-effector domain (DED) of caspase 8. Studies of FLASH protein suggested that this protein may be a component of the death-inducing signaling complex that includes Fas receptor, Fas-binding adapter FADD, and caspase 8, and plays a regulatory role in Fas-mediated apoptosis. Alternative splicing results in multiple transcript variants encoding the same protein.[provided by RefSeq, Nov 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14013395).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001137667.2. 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
	CASP8AP2	NM_001137667.2	MANE Select	c.892A>T	p.Thr298Ser	missense	Exon 7 of 10	NP_001131139.1	Q9UKL3
	CASP8AP2	NM_001137668.2		c.892A>T	p.Thr298Ser	missense	Exon 7 of 10	NP_001131140.1	Q9UKL3
	CASP8AP2	NM_012115.4		c.892A>T	p.Thr298Ser	missense	Exon 7 of 10	NP_036247.1	Q9UKL3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASP8AP2	ENST00000551025.4	TSL:1	c.892A>T	p.Thr298Ser	missense	Exon 7 of 9	ENSP00000478179.2	A0A087WTW5
	CASP8AP2	ENST00000552401.5	TSL:1	c.892A>T	p.Thr298Ser	missense	Exon 7 of 7	ENSP00000485346.1	A0A096LP21
	CASP8AP2	ENST00000419040.6	TSL:2	c.892A>T	p.Thr298Ser	missense	Exon 7 of 7	ENSP00000485349.1	A0A096LP21

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	0.58
DANN	Benign	0.74
DEOGEN2	Benign	0.012	T
FATHMM_MKL	Benign	0.68	D
LIST_S2	Benign	0.64	T
MetaRNN	Benign	0.14	T
PhyloP100		-0.30
PrimateAI	Benign	0.29	T
Sift4G	Benign	0.99	T
MVP		0.76
GERP RS		-2.2
gMVP		0.026

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

hg19: chr6-90572320;