rs16881983

Positions:

• chr6-89606052-C-G
• chr6-89606052-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001242809.2(ANKRD6):​c.364C>G​(p.Gln122Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0297 in 1,595,912 control chromosomes in the GnomAD database, including 1,446 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.037 (155 hom., cov: 33)
  • Exomes 𝑓: 0.029 (1291 hom.)
• Consequence: ANKRD6 NM_001242809.2 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 7.57

Genes affected

ANKRD6 (HGNC:17280): (ankyrin repeat domain 6) Predicted to be involved in negative regulation of canonical Wnt signaling pathway and positive regulation of JNK cascade. Predicted to act upstream of or within positive regulation of Wnt signaling pathway, planar cell polarity pathway. Located in intracellular membrane-bounded organelle. [provided by Alliance of Genome Resources, Apr 2022]

LYRM2 (HGNC:25229): (LYR motif containing 2)

LOC124901359 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.001758337).
• BP6: Variant 6-89606052-C-G is Benign according to our data. Variant chr6-89606052-C-G is described in ClinVar as [Benign]. Clinvar id is 3041275.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.122 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANKRD6	NM_001242809.2	c.364C>G	p.Gln122Glu	missense_variant	5/16	ENST00000339746.9
LOC124901359	XR_007059673.1	n.206-121G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANKRD6	ENST00000339746.9	c.364C>G	p.Gln122Glu	missense_variant	5/16	1	NM_001242809.2	A1

Frequencies

GnomAD3 genomes AF: 0.0366 AC: 5567 AN: 152114 Hom.: 157 Cov.: 33

Gnomad AFR AF: 0.0588

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.0240

Gnomad ASJ AF: 0.0651

Gnomad EAS AF: 0.0422

Gnomad SAS AF: 0.131

Gnomad FIN AF: 0.0229

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0199

Gnomad OTH AF: 0.0363

GnomAD3 exomes AF: 0.0417 AC: 9355 AN: 224118 Hom.: 387 AF XY: 0.0447 AC XY: 5380 AN XY: 120462

Gnomad AFR exome AF: 0.0572

Gnomad AMR exome AF: 0.0305

Gnomad ASJ exome AF: 0.0635

Gnomad EAS exome AF: 0.0406

Gnomad SAS exome AF: 0.134

Gnomad FIN exome AF: 0.0263

Gnomad NFE exome AF: 0.0205

Gnomad OTH exome AF: 0.0366

GnomAD4 exome AF: 0.0290 AC: 41813 AN: 1443680 Hom.: 1291 Cov.: 28 AF XY: 0.0315 AC XY: 22526 AN XY: 716074

Gnomad4 AFR exome AF: 0.0655

Gnomad4 AMR exome AF: 0.0305

Gnomad4 ASJ exome AF: 0.0619

Gnomad4 EAS exome AF: 0.0310

Gnomad4 SAS exome AF: 0.125

Gnomad4 FIN exome AF: 0.0263

Gnomad4 NFE exome AF: 0.0194

Gnomad4 OTH exome AF: 0.0377

GnomAD4 genome AF: 0.0367 AC: 5582 AN: 152232 Hom.: 155 Cov.: 33 AF XY: 0.0386 AC XY: 2875 AN XY: 74428

Gnomad4 AFR AF: 0.0589

Gnomad4 AMR AF: 0.0239

Gnomad4 ASJ AF: 0.0651

Gnomad4 EAS AF: 0.0417

Gnomad4 SAS AF: 0.130

Gnomad4 FIN AF: 0.0229

Gnomad4 NFE AF: 0.0199

Gnomad4 OTH AF: 0.0397

Alfa AF: 0.0227 Hom.: 47

Bravo AF: 0.0364

TwinsUK AF: 0.0165 AC: 61

ALSPAC AF: 0.0163 AC: 63

ESP6500AA AF: 0.0567 AC: 231

ESP6500EA AF: 0.0211 AC: 177

ExAC AF: 0.0405 AC: 4885

Asia WGS AF: 0.109 AC: 380 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

ANKRD6-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 19, 2020

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.28
CADD	Uncertain	24
DANN	Uncertain	0.99
Eigen	Benign	-0.019
Eigen_PC	Benign	0.18
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	D;.;D;D;D;D
MetaRNN	Benign	0.0018	T;T;T;T;T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	-1.2	N;N;N;.;N;.
MutationTaster	Benign	1.0	D;D;D;D;D;D
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-0.86	N;N;N;N;N;N
REVEL	Benign	0.20
Sift	Benign	0.43	T;T;T;T;T;T
Sift4G	Benign	0.72	T;T;T;T;T;T
Polyphen		0.83	P;P;.;.;P;.
Vest4		0.49
MPC		0.23
ClinPred		0.035	T
GERP RS		5.0
Varity_R		0.14
gMVP		0.36

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: rs16881983; hg19: chr6-90315771;