2-97224796-A-ATTTTTTTTT

Variant names:

• chr2-97224796-A-ATTTTTTTTT
• rs201455768
• NM_001354587.1:c.3878-3_3878-2insTTTTTTTTT

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PVS1_Moderate PM2

The NM_001354587.1(ANKRD36):​c.3878-3_3878-2insTTTTTTTTT variant causes a splice acceptor, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 29)
• Consequence: ANKRD36 NM_001354587.1 splice_acceptor, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0630
• Publications: 0 publications found

Genes affected

ANKRD36 (HGNC:24079): (ankyrin repeat domain 36)

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PVS1: Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.012874044 fraction of the gene. Cryptic splice site detected, with MaxEntScore 8, offset of 0 (no position change), new splice context is: aattttttttttttttttAGcag. Cryptic site results in inframe change. If cryptic site found is not functional and variant results in exon loss, it results in frameshift change.
• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001354587.1. 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
	ANKRD36	NM_001354587.1	MANE Select	c.3878-3_3878-2insTTTTTTTTT		splice_acceptor intron	N/A	NP_001341516.1	A6QL64-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKRD36	ENST00000420699.9	TSL:5 MANE Select	c.3878-10_3878-9insTTTTTTTTT		intron	N/A	ENSP00000391950.4	A6QL64-1
	ANKRD36	ENST00000461153.7	TSL:5	c.3878-10_3878-9insTTTTTTTTT		intron	N/A	ENSP00000419530.3	A6QL64-1
	ANKRD36	ENST00000652721.1		c.3878-10_3878-9insTTTTTTTTT		intron	N/A	ENSP00000498611.1	A6QL64-1

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome Cov.: 24

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.063

Splicing

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

Other links and lift over

dbSNP: rs201455768; hg19: chr2-97890533;