2-189689541-A-T

Variant names:

• chr2-189689541-A-T
• rs144939402
• NM_001378068.1:c.616A>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001378068.1(ANKAR):​c.616A>T​(p.Thr206Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000701 in 1,425,578 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. T206A) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: ANKAR NM_001378068.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.29
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08014235).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKAR	NM_001378068.1	c.616A>T	p.Thr206Ser	missense_variant	Exon 3 of 23	ENST00000684021.1	NP_001364997.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANKAR	ENST00000684021.1	c.616A>T	p.Thr206Ser	missense_variant	Exon 3 of 23		NM_001378068.1	ENSP00000507233.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.01e-7 AC: 1 AN: 1425578 Hom.: 0 Cov.: 31 AF XY: 0.00000141 AC XY: 1 AN XY: 707258

African (AFR) AF: 0.00 AC: 0 AN: 31546

American (AMR) AF: 0.00 AC: 0 AN: 35952

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24346

East Asian (EAS) AF: 0.00 AC: 0 AN: 39120

South Asian (SAS) AF: 0.00 AC: 0 AN: 79908

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52358

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5572

European-Non Finnish (NFE) AF: 9.11e-7 AC: 1 AN: 1098026

Other (OTH) AF: 0.00 AC: 0 AN: 58750

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	16
DANN	Benign	0.92
DEOGEN2	Benign	0.0021	T;T
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.043
FATHMM_MKL	Benign	0.65	D
LIST_S2	Benign	0.52	.;T
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.080	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.57	N;N
PhyloP100		4.3
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	0.30	N;N
REVEL	Benign	0.039
Sift	Benign	0.73	T;T
Sift4G	Benign	0.60	T;T
Polyphen		0.022	B;B
Vest4		0.11
MutPred		0.18		Loss of glycosylation at T206 (P = 0.0444);Loss of glycosylation at T206 (P = 0.0444);
MVP		0.62
MPC		0.11
ClinPred		0.23	T
GERP RS		4.8
Varity_R		0.061
gMVP		0.20
Mutation Taster		=93/7	polymorphism

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

Other links and lift over

dbSNP: rs144939402; hg19: chr2-190554267;