rs2304804

Positions:

• chr10-88823335-T-G

Variant summary

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

The NM_144590.3(ANKRD22):​c.443A>C​(p.Gln148Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0443 in 1,613,796 control chromosomes in the GnomAD database, including 2,894 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.086 (1056 hom., cov: 30)
  • Exomes 𝑓: 0.040 (1838 hom.)
• Consequence: ANKRD22 NM_144590.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.31

Genes affected

ANKRD22 (HGNC:28321): (ankyrin repeat domain 22)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0016914606).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.211 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKRD22	NM_144590.3	c.443A>C	p.Gln148Pro	missense_variant	5/6	ENST00000371930.5	NP_653191.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANKRD22	ENST00000371930.5	c.443A>C	p.Gln148Pro	missense_variant	5/6	1	NM_144590.3	ENSP00000360998.4
ANKRD22	ENST00000476963.1	n.181A>C		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes AF: 0.0858 AC: 13050 AN: 152078 Hom.: 1055 Cov.: 30

Gnomad AFR AF: 0.215

Gnomad AMI AF: 0.114

Gnomad AMR AF: 0.0527

Gnomad ASJ AF: 0.0553

Gnomad EAS AF: 0.00405

Gnomad SAS AF: 0.0271

Gnomad FIN AF: 0.0194

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0372

Gnomad OTH AF: 0.0741

GnomAD3 exomes AF: 0.0444 AC: 11177 AN: 251472 Hom.: 543 AF XY: 0.0410 AC XY: 5572 AN XY: 135912

Gnomad AFR exome AF: 0.213

Gnomad AMR exome AF: 0.0394

Gnomad ASJ exome AF: 0.0568

Gnomad EAS exome AF: 0.00343

Gnomad SAS exome AF: 0.0255

Gnomad FIN exome AF: 0.0191

Gnomad NFE exome AF: 0.0371

Gnomad OTH exome AF: 0.0495

GnomAD4 exome AF: 0.0400 AC: 58406 AN: 1461600 Hom.: 1838 Cov.: 31 AF XY: 0.0392 AC XY: 28488 AN XY: 727122

Gnomad4 AFR exome AF: 0.217

Gnomad4 AMR exome AF: 0.0425

Gnomad4 ASJ exome AF: 0.0556

Gnomad4 EAS exome AF: 0.0111

Gnomad4 SAS exome AF: 0.0252

Gnomad4 FIN exome AF: 0.0193

Gnomad4 NFE exome AF: 0.0364

Gnomad4 OTH exome AF: 0.0518

GnomAD4 genome AF: 0.0859 AC: 13073 AN: 152196 Hom.: 1056 Cov.: 30 AF XY: 0.0828 AC XY: 6163 AN XY: 74408

Gnomad4 AFR AF: 0.215

Gnomad4 AMR AF: 0.0526

Gnomad4 ASJ AF: 0.0553

Gnomad4 EAS AF: 0.00406

Gnomad4 SAS AF: 0.0269

Gnomad4 FIN AF: 0.0194

Gnomad4 NFE AF: 0.0372

Gnomad4 OTH AF: 0.0733

Alfa AF: 0.0492 Hom.: 677

Bravo AF: 0.0934

TwinsUK AF: 0.0453 AC: 168

ALSPAC AF: 0.0397 AC: 153

ESP6500AA AF: 0.192 AC: 844

ESP6500EA AF: 0.0406 AC: 349

ExAC AF: 0.0469 AC: 5688

Asia WGS AF: 0.0300 AC: 105 AN: 3478

EpiCase AF: 0.0416

EpiControl AF: 0.0405

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0050	T
Eigen	Benign	-0.082
Eigen_PC	Benign	0.016
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Benign	0.78	T
MetaRNN	Benign	0.0017	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.10	N
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.055
Sift	Benign	0.18	T
Sift4G	Benign	0.32	T
Polyphen		0.75	P
Vest4		0.18
MPC		0.54
ClinPred		0.024	T
GERP RS		3.3
Varity_R		0.45
gMVP		0.66

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: rs2304804; hg19: chr10-90583092;