rs201455768

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr2-97224796-A-AT
• chr2-97224796-A-ATT
• chr2-97224796-A-ATTTTTTTTT

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 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 VariationId is 2858945.Status of the report is criteria_provided_single_submitter, 1 stars.

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.3878-3dupT		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_3878-9insT		intron	N/A	ENSP00000391950.4	A6QL64-1
	ANKRD36	ENST00000461153.7	TSL:5	c.3878-10_3878-9insT		intron	N/A	ENSP00000419530.3	A6QL64-1
	ANKRD36	ENST00000652721.1		c.3878-10_3878-9insT		intron	N/A	ENSP00000498611.1	A6QL64-1

Frequencies

GnomAD3 genomes AF: 0.0494 AC: 5358 AN: 108458 Hom.: 378 Cov.: 29

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

GnomAD2 exomes AF: 0.0000165 AC: 1 AN: 60614 AF XY: 0.0000334

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 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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0342 AC: 522 AN: 15246

American (AMR) AF: 0.0187 AC: 414 AN: 22082

Ashkenazi Jewish (ASJ) AF: 0.00794 AC: 158 AN: 19894

East Asian (EAS) AF: 0.0228 AC: 417 AN: 18304

South Asian (SAS) AF: 0.0211 AC: 786 AN: 37180

European-Finnish (FIN) AF: 0.000797 AC: 38 AN: 47654

Middle Eastern (MID) AF: 0.00596 AC: 18 AN: 3022

European-Non Finnish (NFE) AF: 0.00120 AC: 1110 AN: 923382

Other (OTH) AF: 0.00478 AC: 214 AN: 44776

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

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

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.178 AC: 3832 AN: 21492

American (AMR) AF: 0.0345 AC: 334 AN: 9688

Ashkenazi Jewish (ASJ) AF: 0.0294 AC: 72 AN: 2450

East Asian (EAS) AF: 0.118 AC: 274 AN: 2320

South Asian (SAS) AF: 0.111 AC: 208 AN: 1866

European-Finnish (FIN) AF: 0.000826 AC: 8 AN: 9688

Middle Eastern (MID) AF: 0.0253 AC: 5 AN: 198

European-Non Finnish (NFE) AF: 0.00936 AC: 548 AN: 58556

Other (OTH) AF: 0.0472 AC: 70 AN: 1482

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00730 Hom.: 21

Asia WGS AF: 0.335 AC: 885 AN: 2648

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.063
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs201455768; hg19: chr2-97890533;