10-88822973-G-C

Position:

• chr10-88822973-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_144590.3(ANKRD22):​c.544C>G​(p.Gln182Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 30)
• Consequence: ANKRD22 NM_144590.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.17

Genes affected

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

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1524849).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKRD22	NM_144590.3	c.544C>G	p.Gln182Glu	missense_variant	6/6	ENST00000371930.5	NP_653191.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANKRD22	ENST00000371930.5	c.544C>G	p.Gln182Glu	missense_variant	6/6	1	NM_144590.3	ENSP00000360998	P1
ANKRD22	ENST00000476963.1	n.282C>G		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 30

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 20, 2023

The c.544C>G (p.Q182E) alteration is located in exon 6 (coding exon 6) of the ANKRD22 gene. This alteration results from a C to G substitution at nucleotide position 544, causing the glutamine (Q) at amino acid position 182 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Uncertain	23
DANN	Benign	0.96
DEOGEN2	Benign	0.00011	T
Eigen	Benign	-0.016
Eigen_PC	Benign	0.20
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-0.15	N
MutationTaster	Benign	0.86	D
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.28	N
REVEL	Benign	0.16
Sift	Benign	0.67	T
Sift4G	Benign	0.67	T
Polyphen		0.83	P
Vest4		0.15
MutPred		0.35		Gain of disorder (P = 0.034);
MVP		0.39
MPC		0.19
ClinPred		0.74	D
GERP RS		5.7
Varity_R		0.12
gMVP		0.26

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

LitVar

Other links and lift over

dbSNP: rs1035665873; hg19: chr10-90582730;