rs2899293

Positions:

• chr22-37846806-G-A
• chr22-37846806-G-C
• chr22-37846806-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001349853.2(ANKRD54):​c.133+1423C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.592 in 151,552 control chromosomes in the GnomAD database, including 26,823 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.59 (26823 hom., cov: 31)
• Consequence: ANKRD54 NM_001349853.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.28

Genes affected

ANKRD54 (HGNC:25185): (ankyrin repeat domain 54) Predicted to enable protein kinase regulator activity. Predicted to be involved in positive regulation of erythrocyte differentiation; regulation of intracellular signal transduction; and regulation of protein kinase activity. Predicted to act upstream of or within nucleocytoplasmic transport. Predicted to be located in midbody. Predicted to be active in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.839 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKRD54	NM_001349853.2	c.133+1423C>T		intron_variant			NP_001336782.1
ANKRD54	XM_047441138.1	c.133+1423C>T		intron_variant			XP_047297094.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANKRD54	ENST00000609454.5	c.-28+2131C>T		intron_variant		3		ENSP00000477088

Frequencies

GnomAD3 genomes AF: 0.592 AC: 89646 AN: 151440 Hom.: 26811 Cov.: 31

Gnomad AFR AF: 0.562

Gnomad AMI AF: 0.535

Gnomad AMR AF: 0.591

Gnomad ASJ AF: 0.564

Gnomad EAS AF: 0.860

Gnomad SAS AF: 0.652

Gnomad FIN AF: 0.574

Gnomad MID AF: 0.561

Gnomad NFE AF: 0.591

Gnomad OTH AF: 0.583

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.592 AC: 89703 AN: 151552 Hom.: 26823 Cov.: 31 AF XY: 0.592 AC XY: 43777 AN XY: 73996

Gnomad4 AFR AF: 0.562

Gnomad4 AMR AF: 0.591

Gnomad4 ASJ AF: 0.564

Gnomad4 EAS AF: 0.860

Gnomad4 SAS AF: 0.653

Gnomad4 FIN AF: 0.574

Gnomad4 NFE AF: 0.591

Gnomad4 OTH AF: 0.585

Alfa AF: 0.588 Hom.: 44313

Bravo AF: 0.593

Asia WGS AF: 0.710 AC: 2470 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.1
DANN	Benign	0.52

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2899293; hg19: chr22-38242813;