chr2-97224796-A-ATTTTTTTTT

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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

Genes affected

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

ACMG classification

Verdict is Uncertain_significance. Variant got 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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKRD36	NM_001354587.1	c.3878-3_3878-2insTTTTTTTTT		splice_acceptor_variant, intron_variant	Intron 66 of 75	ENST00000420699.9	NP_001341516.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANKRD36	ENST00000420699.9	c.3878-10_3878-9insTTTTTTTTT		intron_variant	Intron 66 of 75	5	NM_001354587.1	ENSP00000391950.4
ANKRD36	ENST00000461153.7	c.3878-10_3878-9insTTTTTTTTT		intron_variant	Intron 66 of 74	5		ENSP00000419530.3
ANKRD36	ENST00000652721.1	c.3878-10_3878-9insTTTTTTTTT		intron_variant	Intron 66 of 75			ENSP00000498611.1
ANKRD36	ENST00000421946.2	n.1101-13_1101-12insTTTTTTTTT		intron_variant	Intron 8 of 13	2

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome Cov.: 24

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs201455768; hg19: chr2-97890533;