2-189693168-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001378068.1(ANKAR):c.1298A>G(p.His433Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00156 in 1,552,386 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0011 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0016 (13 hom.)
• Consequence: ANKAR NM_001378068.1 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.15

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 Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.009365529).
• BP6: Variant 2-189693168-A-G is Benign according to our data. Variant chr2-189693168-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2651760.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANKAR	NM_001378068.1	c.1298A>G	p.His433Arg	missense_variant	5/23	ENST00000684021.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANKAR	ENST00000684021.1	c.1298A>G	p.His433Arg	missense_variant	5/23		NM_001378068.1	P1

Frequencies

GnomAD3 genomes AF: 0.00105 AC: 160 AN: 152222 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000217

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000982

Gnomad ASJ AF: 0.00432

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00372

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00143

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.00148 AC: 336 AN: 226342 Hom.: 4 AF XY: 0.00171 AC XY: 211 AN XY: 123408

Gnomad AFR exome AF: 0.000270

Gnomad AMR exome AF: 0.000419

Gnomad ASJ exome AF: 0.00461

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00512

Gnomad FIN exome AF: 0.000189

Gnomad NFE exome AF: 0.00127

Gnomad OTH exome AF: 0.00109

GnomAD4 exome AF: 0.00162 AC: 2263 AN: 1400046 Hom.: 13 Cov.: 26 AF XY: 0.00172 AC XY: 1205 AN XY: 698630

Gnomad4 AFR exome AF: 0.000260

Gnomad4 AMR exome AF: 0.000499

Gnomad4 ASJ exome AF: 0.00425

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00514

Gnomad4 FIN exome AF: 0.000339

Gnomad4 NFE exome AF: 0.00149

Gnomad4 OTH exome AF: 0.00137

GnomAD4 genome AF: 0.00105 AC: 160 AN: 152340 Hom.: 1 Cov.: 32 AF XY: 0.00102 AC XY: 76 AN XY: 74492

Gnomad4 AFR AF: 0.000216

Gnomad4 AMR AF: 0.000981

Gnomad4 ASJ AF: 0.00432

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00373

Gnomad4 FIN AF: 0.0000941

Gnomad4 NFE AF: 0.00143

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.00145 Hom.: 0

Bravo AF: 0.000986

TwinsUK AF: 0.00162 AC: 6

ALSPAC AF: 0.00182 AC: 7

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.00117 AC: 10

ExAC AF: 0.00149 AC: 181

Asia WGS AF: 0.000867 AC: 4 AN: 3474

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2022

ANKAR: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.61
Cadd	Benign	17
Dann	Benign	0.94
DEOGEN2	Benign	0.0042	T;T
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.16
FATHMM_MKL	Benign	0.71	D
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.0094	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N;N
MutationTaster	Benign	1.0	N;N;N;N;N
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.75	N;N
REVEL	Benign	0.12
Sift	Benign	0.10	T;T
Sift4G	Benign	0.15	T;T
Vest4		0.14
MVP		0.68
MPC		0.13
ClinPred		0.016	T
GERP RS		4.8
Varity_R		0.076
gMVP		0.40

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

LitVar

Other links and lift over

dbSNP: rs148779806; hg19: chr2-190557894; COSMIC: COSV104385741; COSMIC: COSV104385741;