2-189689587-A-G

Variant names:

• chr2-189689587-A-G
• rs2036113204
• NM_001378068.1:c.662A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001378068.1(ANKAR):​c.662A>G​(p.Glu221Gly) 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. 14/22 in silico tools predict 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: 0.906
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06303769).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001378068.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKAR	NM_001378068.1	MANE Select	c.662A>G	p.Glu221Gly	missense	Exon 3 of 23	NP_001364997.1	Q7Z5J8-1
	ANKAR	NM_144708.3		c.662A>G	p.Glu221Gly	missense	Exon 3 of 23	NP_653309.3	Q7Z5J8-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKAR	ENST00000684021.1	MANE Select	c.662A>G	p.Glu221Gly	missense	Exon 3 of 23	ENSP00000507233.1	Q7Z5J8-1
	ANKAR	ENST00000313581.4	TSL:1	c.662A>G	p.Glu221Gly	missense	Exon 2 of 22	ENSP00000313513.4	Q7Z5J8-1
	ANKAR	ENST00000520309.5	TSL:5	c.662A>G	p.Glu221Gly	missense	Exon 3 of 23	ENSP00000427882.1	Q7Z5J8-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0040	T
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.17
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.0086	T
MetaRNN	Benign	0.063	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		0.91
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.0090
Sift	Benign	0.49	T
Sift4G	Benign	0.48	T
Polyphen		0.10	B
Vest4		0.13
MutPred		0.33		Loss of stability (P = 0.0625)
MVP		0.67
MPC		0.14
ClinPred		0.19	T
GERP RS		2.1
Varity_R		0.095
gMVP		0.35
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

dbSNP: rs2036113204; hg19: chr2-190554313;