6-89606052-C-G

Variant names:

• chr6-89606052-C-G
• rs16881983
• NM_001242809.2:c.364C>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 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. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.037 (155 hom., cov: 33)
  • Exomes 𝑓: 0.029 (1291 hom.)
• Consequence: ANKRD6 NM_001242809.2 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 7.57
• Publications: 8 publications found

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

Our verdict: Benign. The variant received -13 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 VariationId is 3041275.Status of the report is no_assertion_criteria_provided, 0 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 rank	MANE	Protein	UniProt
ANKRD6	NM_001242809.2	c.364C>G	p.Gln122Glu	missense_variant	Exon 5 of 16	ENST00000339746.9	NP_001229738.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANKRD6	ENST00000339746.9	c.364C>G	p.Gln122Glu	missense_variant	Exon 5 of 16	1	NM_001242809.2	ENSP00000345767.4

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

GnomAD2 exomes AF: 0.0417 AC: 9355 AN: 224118 AF XY: 0.0447

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 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

African (AFR) AF: 0.0655 AC: 2175 AN: 33206

American (AMR) AF: 0.0305 AC: 1299 AN: 42564

Ashkenazi Jewish (ASJ) AF: 0.0619 AC: 1590 AN: 25700

East Asian (EAS) AF: 0.0310 AC: 1214 AN: 39106

South Asian (SAS) AF: 0.125 AC: 10277 AN: 82286

European-Finnish (FIN) AF: 0.0263 AC: 1379 AN: 52376

Middle Eastern (MID) AF: 0.0358 AC: 205 AN: 5732

European-Non Finnish (NFE) AF: 0.0194 AC: 21422 AN: 1103002

Other (OTH) AF: 0.0377 AC: 2252 AN: 59708

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

African (AFR) AF: 0.0589 AC: 2448 AN: 41530

American (AMR) AF: 0.0239 AC: 366 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0651 AC: 226 AN: 3470

East Asian (EAS) AF: 0.0417 AC: 216 AN: 5178

South Asian (SAS) AF: 0.130 AC: 626 AN: 4818

European-Finnish (FIN) AF: 0.0229 AC: 243 AN: 10604

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0199 AC: 1353 AN: 68020

Other (OTH) AF: 0.0397 AC: 84 AN: 2114

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: no assertion criteria provided

Submissions by phenotype

ANKRD6-related disorder Benign:1

Feb 19, 2020

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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
DEOGEN2	Benign	0.0017	.;T;.;T;T;T
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;.
PhyloP100		7.6
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
Mutation Taster		=62/38	polymorphism (auto)

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: rs16881983; hg19: chr6-90315771; COSMIC: COSV107409356; COSMIC: COSV107409356;