chr10-27053384-T-G

Variant names:

• chr10-27053384-T-G
• NM_014915.3:c.1571A>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014915.3(ANKRD26):​c.1571A>C​(p.His524Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,458,012 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: ANKRD26 NM_014915.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.185

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.029448688).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKRD26	NM_014915.3	c.1571A>C	p.His524Pro	missense_variant	Exon 16 of 34	ENST00000376087.5	NP_055730.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANKRD26	ENST00000376087.5	c.1571A>C	p.His524Pro	missense_variant	Exon 16 of 34	5	NM_014915.3	ENSP00000365255.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1458012 Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1 AN XY: 725386

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.01e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	1.4
DANN	Benign	0.16
DEOGEN2	Benign	0.025	.;T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.0049	N
LIST_S2	Benign	0.42	T;T
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.029	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.26	.;N
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.70	N;N
REVEL	Benign	0.021
Sift	Benign	0.30	T;T
Sift4G	Benign	0.32	T;T
Polyphen		0.0	.;B
Vest4		0.11
MutPred		0.20		.;Gain of relative solvent accessibility (P = 0.005);
MVP		0.088
MPC		0.066
ClinPred		0.18	T
GERP RS		-7.3
Varity_R		0.052
gMVP		0.013

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-27342313;