2-189677066-C-A

Variant names:

• chr2-189677066-C-A
• rs556471471
• NM_001378068.1:c.576C>A

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.576C>A​(p.Asp192Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000707 in 1,413,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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 Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: ANKAR NM_001378068.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.966
• 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=0.05733663).

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.576C>A	p.Asp192Glu	missense	Exon 2 of 23	NP_001364997.1	Q7Z5J8-1
	ANKAR	NM_144708.3		c.576C>A	p.Asp192Glu	missense	Exon 2 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.576C>A	p.Asp192Glu	missense	Exon 2 of 23	ENSP00000507233.1	Q7Z5J8-1
	ANKAR	ENST00000313581.4	TSL:1	c.576C>A	p.Asp192Glu	missense	Exon 1 of 22	ENSP00000313513.4	Q7Z5J8-1
	ANKAR	ENST00000520309.5	TSL:5	c.576C>A	p.Asp192Glu	missense	Exon 2 of 23	ENSP00000427882.1	Q7Z5J8-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.07e-7 AC: 1 AN: 1413890 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 701456

African (AFR) AF: 0.0000321 AC: 1 AN: 31170

American (AMR) AF: 0.00 AC: 0 AN: 33714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23326

East Asian (EAS) AF: 0.00 AC: 0 AN: 39418

South Asian (SAS) AF: 0.00 AC: 0 AN: 79614

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48128

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5522

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1094764

Other (OTH) AF: 0.00 AC: 0 AN: 58234

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	2.2
DANN	Benign	0.96
DEOGEN2	Benign	0.0033	T
Eigen	Benign	-0.99
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.099	N
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.0091	T
MetaRNN	Benign	0.057	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		-0.97
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.58	N
REVEL	Benign	0.054
Sift	Benign	0.16	T
Sift4G	Benign	0.20	T
Polyphen		0.19	B
Vest4		0.16
MutPred		0.13		Gain of helix (P = 0.132)
MVP		0.44
MPC		0.096
ClinPred		0.10	T
GERP RS		-2.4
Varity_R		0.046
gMVP		0.17
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: rs556471471; hg19: chr2-190541792;