2-189694986-A-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001378068.1(ANKAR):c.1313A>C(p.Tyr438Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00121 in 1,500,866 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0063 (9 hom., cov: 32)
  • Exomes 𝑓: 0.00063 (12 hom.)
• Consequence: ANKAR NM_001378068.1 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.78

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.009079933).
• BP6: Variant 2-189694986-A-C is Benign according to our data. Variant chr2-189694986-A-C is described in ClinVar as [Benign]. Clinvar id is 785983.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00631 (961/152280) while in subpopulation AFR AF= 0.022 (914/41568). AF 95% confidence interval is 0.0208. There are 9 homozygotes in gnomad4. There are 447 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANKAR	NM_001378068.1	c.1313A>C	p.Tyr438Ser	missense_variant	6/23	ENST00000684021.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANKAR	ENST00000684021.1	c.1313A>C	p.Tyr438Ser	missense_variant	6/23		NM_001378068.1	P1

Frequencies

GnomAD3 genomes AF: 0.00632 AC: 961 AN: 152162 Hom.: 9 Cov.: 32

Gnomad AFR AF: 0.0221

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00223

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00478

GnomAD3 exomes AF: 0.00154 AC: 313 AN: 203450 Hom.: 4 AF XY: 0.00113 AC XY: 126 AN XY: 111340

Gnomad AFR exome AF: 0.0211

Gnomad AMR exome AF: 0.000733

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000434

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000307

Gnomad OTH exome AF: 0.000854

GnomAD4 exome AF: 0.000630 AC: 850 AN: 1348586 Hom.: 12 Cov.: 29 AF XY: 0.000573 AC XY: 381 AN XY: 664372

Gnomad4 AFR exome AF: 0.0235

Gnomad4 AMR exome AF: 0.00122

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000158

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000142

Gnomad4 OTH exome AF: 0.00130

GnomAD4 genome AF: 0.00631 AC: 961 AN: 152280 Hom.: 9 Cov.: 32 AF XY: 0.00600 AC XY: 447 AN XY: 74468

Gnomad4 AFR AF: 0.0220

Gnomad4 AMR AF: 0.00223

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.00473

Alfa AF: 0.000533 Hom.: 1

Bravo AF: 0.00673

ESP6500AA AF: 0.0173 AC: 76

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00171 AC: 208

Asia WGS AF: 0.000867 AC: 3 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Oct 24, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.31
Cadd	Uncertain	25
Dann	Uncertain	0.99
DEOGEN2	Benign	0.012	T;T
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Uncertain	0.93	D
MetaRNN	Benign	0.0091	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.5	M;M
MutationTaster	Benign	0.98	D;D;D;D;D
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-2.3	N;N
REVEL	Benign	0.21
Sift	Benign	0.18	T;T
Sift4G	Benign	0.087	T;T
Vest4		0.73
MVP		0.60
MPC		0.39
ClinPred		0.042	T
GERP RS		5.9
Varity_R		0.23
gMVP		0.73

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: rs115747871; hg19: chr2-190559712; COSMIC: COSV99029166; COSMIC: COSV99029166;