chr2-189677050-C-T

Variant names:

• chr2-189677050-C-T
• rs374314519
• NM_001378068.1:c.560C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001378068.1(ANKAR):​c.560C>T​(p.Pro187Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000472 in 1,587,678 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000039 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000048 (0 hom.)
• Consequence: ANKAR NM_001378068.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.48
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32946578).

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.560C>T	p.Pro187Leu	missense	Exon 2 of 23	NP_001364997.1	Q7Z5J8-1
	ANKAR	NM_144708.3		c.560C>T	p.Pro187Leu	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.560C>T	p.Pro187Leu	missense	Exon 2 of 23	ENSP00000507233.1	Q7Z5J8-1
	ANKAR	ENST00000313581.4	TSL:1	c.560C>T	p.Pro187Leu	missense	Exon 1 of 22	ENSP00000313513.4	Q7Z5J8-1
	ANKAR	ENST00000520309.5	TSL:5	c.560C>T	p.Pro187Leu	missense	Exon 2 of 23	ENSP00000427882.1	Q7Z5J8-1

Frequencies

GnomAD3 genomes AF: 0.0000394 AC: 6 AN: 152130 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000226 AC: 5 AN: 221448 AF XY: 0.0000248

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000489

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000481 AC: 69 AN: 1435548 Hom.: 0 Cov.: 31 AF XY: 0.0000490 AC XY: 35 AN XY: 713628

African (AFR) AF: 0.00 AC: 0 AN: 31864

American (AMR) AF: 0.00 AC: 0 AN: 37456

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24472

East Asian (EAS) AF: 0.00 AC: 0 AN: 39556

South Asian (SAS) AF: 0.00 AC: 0 AN: 82934

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51040

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5630

European-Non Finnish (NFE) AF: 0.0000625 AC: 69 AN: 1103500

Other (OTH) AF: 0.00 AC: 0 AN: 59096

GnomAD4 genome AF: 0.0000394 AC: 6 AN: 152130 Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2 AN XY: 74318

African (AFR) AF: 0.00 AC: 0 AN: 41420

American (AMR) AF: 0.00 AC: 0 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10592

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.000152 Hom.: 0

Bravo AF: 0.0000529

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00000825 AC: 1

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	0.20
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.32
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.041	T
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.033	D
MetaRNN	Benign	0.33	T
MetaSVM	Benign	-0.73	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		4.5
PrimateAI	Uncertain	0.50	T
PROVEAN	Uncertain	-3.5	D
REVEL	Benign	0.15
Sift	Uncertain	0.011	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.91	P
Vest4		0.49
MVP		0.73
MPC		0.37
ClinPred		0.77	D
GERP RS		5.5
Varity_R		0.16
gMVP		0.62
Mutation Taster		=77/23	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: rs374314519; hg19: chr2-190541776;