2-97224796-A-AT

Variant names:

• chr2-97224796-A-AT
• rs201455768
• NM_001354587.1:c.3878-3dupT

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PVS1_Moderate BP6_Moderate

The NM_001354587.1(ANKRD36):​c.3878-3dupT variant causes a splice acceptor, intron change involving the alteration of a non-conserved nucleotide. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.049 (379 hom., cov: 29)
  • Exomes 𝑓: 0.0032 (403 hom.)
  • Failed GnomAD Quality Control
• Consequence: ANKRD36 NM_001354587.1 splice_acceptor, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0630

Genes affected

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

ACMG classification

Verdict is Uncertain_significance. Variant got 0 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 4, offset of 0 (no position change), new splice context is: aaatatataattttttttAGcag. Cryptic site results in inframe change. If cryptic site found is not functional and variant results in exon loss, it results in frameshift change.
• BP6: Variant 2-97224796-A-AT is Benign according to our data. Variant chr2-97224796-A-AT is described in ClinVar as [Benign]. Clinvar id is 2858945.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.00 AC: 5358 AN: 108458 Hom.: 378 Cov.: 29 FAILED QC

Gnomad AFR AF: 0.179

Gnomad AMI AF: 0.0131

Gnomad AMR AF: 0.0345

Gnomad ASJ AF: 0.0294

Gnomad EAS AF: 0.119

Gnomad SAS AF: 0.113

Gnomad FIN AF: 0.000826

Gnomad MID AF: 0.0229

Gnomad NFE AF: 0.00938

Gnomad OTH AF: 0.0459

GnomAD3 exomes AF: 0.0000165 AC: 1 AN: 60614 Hom.: 0 AF XY: 0.0000334 AC XY: 1 AN XY: 29978

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000320

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00325 AC: 3677 AN: 1131540 Hom.: 403 Cov.: 24 AF XY: 0.00365 AC XY: 2031 AN XY: 556388

Gnomad4 AFR exome AF: 0.0342

Gnomad4 AMR exome AF: 0.0187

Gnomad4 ASJ exome AF: 0.00794

Gnomad4 EAS exome AF: 0.0228

Gnomad4 SAS exome AF: 0.0211

Gnomad4 FIN exome AF: 0.000797

Gnomad4 NFE exome AF: 0.00120

Gnomad4 OTH exome AF: 0.00478

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0494 AC: 5361 AN: 108502 Hom.: 379 Cov.: 29 AF XY: 0.0465 AC XY: 2454 AN XY: 52812

Gnomad4 AFR AF: 0.178

Gnomad4 AMR AF: 0.0345

Gnomad4 ASJ AF: 0.0294

Gnomad4 EAS AF: 0.118

Gnomad4 SAS AF: 0.111

Gnomad4 FIN AF: 0.000826

Gnomad4 NFE AF: 0.00936

Gnomad4 OTH AF: 0.0472

Alfa AF: 0.00730 Hom.: 21

Asia WGS AF: 0.335 AC: 885 AN: 2648

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Oct 02, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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;