chr10-27100510-C-A

Position:

• chr10-27100510-C-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The 10-27100510-C-A variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00478 in 885,920 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0049 (3 hom., cov: 34)
  • Exomes 𝑓: 0.0048 (23 hom.)
• Consequence: ANKRD26 NM_014915.3 upstream_gene
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.80

Genes affected

ANKRD26 (HGNC:29186): (ankyrin repeat domain containing 26) This gene encodes a protein containing N-terminal ankyrin repeats which function in protein-protein interactions. Mutations in this gene are associated with autosomal dominant thrombocytopenia-2. Pseudogenes of this gene are found on chromosome 7, 10, 13 and 16. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 10-27100510-C-A is Benign according to our data. Variant chr10-27100510-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 434211.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00493 (751/152376) while in subpopulation NFE AF= 0.00563 (383/68034). AF 95% confidence interval is 0.00516. There are 3 homozygotes in gnomad4. There are 449 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 751 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKRD26	NM_014915.3			upstream_gene_variant		ENST00000376087.5	NP_055730.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANKRD26	ENST00000376087.5			upstream_gene_variant		5	NM_014915.3	ENSP00000365255	A2
ANKRD26	ENST00000436985.7			upstream_gene_variant		1		ENSP00000405112	P4
ANKRD26	ENST00000676420.1			upstream_gene_variant				ENSP00000502355

Frequencies

GnomAD3 genomes AF: 0.00493 AC: 751 AN: 152258 Hom.: 3 Cov.: 34

Gnomad AFR AF: 0.000772

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.00183

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0272

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00563

Gnomad OTH AF: 0.00335

GnomAD4 exome AF: 0.00475 AC: 3485 AN: 733544 Hom.: 23 Cov.: 10 AF XY: 0.00465 AC XY: 1736 AN XY: 373312

Gnomad4 AFR exome AF: 0.000917

Gnomad4 AMR exome AF: 0.00104

Gnomad4 ASJ exome AF: 0.0000646

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0247

Gnomad4 NFE exome AF: 0.00488

Gnomad4 OTH exome AF: 0.00384

GnomAD4 genome AF: 0.00493 AC: 751 AN: 152376 Hom.: 3 Cov.: 34 AF XY: 0.00603 AC XY: 449 AN XY: 74512

Gnomad4 AFR AF: 0.000769

Gnomad4 AMR AF: 0.00183

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0272

Gnomad4 NFE AF: 0.00563

Gnomad4 OTH AF: 0.00331

Alfa AF: 0.00455 Hom.: 0

Bravo AF: 0.00298

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Oct 25, 2018

- -

Thrombocytopenia 2 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 29, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	2.0
DANN	Benign	0.83

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs527666933; hg19: chr10-27389439;