2-189676531-A-G

Position:

• chr2-189676531-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001378068.1(ANKAR):​c.41A>G​(p.Gln14Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ANKAR NM_001378068.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.52

Genes affected

ANKAR (HGNC:26350): (ankyrin and armadillo repeat containing) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.38901615).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANKAR	NM_001378068.1	c.41A>G	p.Gln14Arg	missense_variant	2/23	ENST00000684021.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANKAR	ENST00000684021.1	c.41A>G	p.Gln14Arg	missense_variant	2/23		NM_001378068.1	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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

Jun 02, 2023

The c.41A>G (p.Q14R) alteration is located in exon 2 (coding exon 1) of the ANKAR gene. This alteration results from a A to G substitution at nucleotide position 41, causing the glutamine (Q) at amino acid position 14 to be replaced by an arginine (R). 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	0.10
BayesDel_addAF	Benign	-0.088	T
BayesDel_noAF	Benign	-0.36
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0056	T;T
Eigen	Uncertain	0.22
Eigen_PC	Uncertain	0.22
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.49	.;T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.39	T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Uncertain	2.1	M;M
MutationTaster	Benign	1.0	D;D;N;N;N
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.54	N;N
REVEL	Benign	0.14
Sift	Benign	0.25	T;T
Sift4G	Pathogenic	0.0	D;D
Polyphen		0.97	D;D
Vest4		0.50
MutPred		0.17		Gain of helix (P = 0.0325);Gain of helix (P = 0.0325);
MVP		0.86
MPC		0.52
ClinPred		0.52	D
GERP RS		5.7
Varity_R		0.078
gMVP		0.37

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: chr2-190541257;