rs2273238

Variant names:

• chr6-89616641-C-T
• rs2273238
• NM_001242809.2:c.698C>T
• ANKRD6 p.Thr233Met

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.698C>T​(p.Thr233Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0726 in 1,613,750 control chromosomes in the GnomAD database, including 9,146 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 Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.14 (2408 hom., cov: 33)
  • Exomes 𝑓: 0.066 (6738 hom.)
• Consequence: ANKRD6 NM_001242809.2 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 1.41
• Publications: 19 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=0.0060423315).
• BP6: Variant 6-89616641-C-T is Benign according to our data. Variant chr6-89616641-C-T is described in ClinVar as Benign. ClinVar VariationId is 3060427.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.289 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001242809.2. 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
	ANKRD6	NM_001242809.2	MANE Select	c.698C>T	p.Thr233Met	missense	Exon 8 of 16	NP_001229738.1	Q9Y2G4-2
	ANKRD6	NM_001242811.1		c.698C>T	p.Thr233Met	missense	Exon 8 of 16	NP_001229740.1	Q9Y2G4-2
	ANKRD6	NM_014942.4		c.698C>T	p.Thr233Met	missense	Exon 8 of 16	NP_055757.3	Q9Y2G4-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKRD6	ENST00000339746.9	TSL:1 MANE Select	c.698C>T	p.Thr233Met	missense	Exon 8 of 16	ENSP00000345767.4	Q9Y2G4-2
	ANKRD6	ENST00000447838.6	TSL:1	c.698C>T	p.Thr233Met	missense	Exon 8 of 16	ENSP00000396771.2	Q9Y2G4-3
	ANKRD6	ENST00000369408.9	TSL:1	c.698C>T	p.Thr233Met	missense	Exon 8 of 15	ENSP00000358416.5	Q9Y2G4-1

Frequencies

GnomAD3 genomes AF: 0.137 AC: 20837 AN: 152136 Hom.: 2401 Cov.: 33

Gnomad AFR AF: 0.293

Gnomad AMI AF: 0.0461

Gnomad AMR AF: 0.159

Gnomad ASJ AF: 0.0952

Gnomad EAS AF: 0.256

Gnomad SAS AF: 0.194

Gnomad FIN AF: 0.0595

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0399

Gnomad OTH AF: 0.121

GnomAD2 exomes AF: 0.115 AC: 28717 AN: 249234 AF XY: 0.110

Gnomad AFR exome AF: 0.296

Gnomad AMR exome AF: 0.198

Gnomad ASJ exome AF: 0.0885

Gnomad EAS exome AF: 0.248

Gnomad FIN exome AF: 0.0623

Gnomad NFE exome AF: 0.0394

Gnomad OTH exome AF: 0.0891

GnomAD4 exome AF: 0.0658 AC: 96227 AN: 1461496 Hom.: 6738 Cov.: 31 AF XY: 0.0683 AC XY: 49631 AN XY: 727010

African (AFR) AF: 0.302 AC: 10090 AN: 33454

American (AMR) AF: 0.194 AC: 8677 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.0883 AC: 2308 AN: 26132

East Asian (EAS) AF: 0.251 AC: 9953 AN: 39694

South Asian (SAS) AF: 0.184 AC: 15862 AN: 86244

European-Finnish (FIN) AF: 0.0595 AC: 3179 AN: 53398

Middle Eastern (MID) AF: 0.0850 AC: 490 AN: 5768

European-Non Finnish (NFE) AF: 0.0363 AC: 40366 AN: 1111728

Other (OTH) AF: 0.0878 AC: 5302 AN: 60362

GnomAD4 genome AF: 0.137 AC: 20876 AN: 152254 Hom.: 2408 Cov.: 33 AF XY: 0.140 AC XY: 10418 AN XY: 74452

African (AFR) AF: 0.293 AC: 12162 AN: 41526

American (AMR) AF: 0.160 AC: 2444 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0952 AC: 330 AN: 3468

East Asian (EAS) AF: 0.258 AC: 1332 AN: 5170

South Asian (SAS) AF: 0.195 AC: 940 AN: 4828

European-Finnish (FIN) AF: 0.0595 AC: 631 AN: 10612

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0399 AC: 2715 AN: 68028

Other (OTH) AF: 0.122 AC: 258 AN: 2112

Alfa AF: 0.0737 Hom.: 3903

Bravo AF: 0.148

Asia WGS AF: 0.234 AC: 810 AN: 3478

EpiCase AF: 0.0427

EpiControl AF: 0.0394

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	ANKRD6-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0057	T
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.59
FATHMM_MKL	Benign	0.42	N
LIST_S2	Benign	0.76	T
MetaRNN	Benign	0.0060	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.46	N
PhyloP100		1.4
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.14
Sift	Benign	0.11	T
Sift4G	Benign	0.14	T
Varity_R		0.016
gMVP		0.25
Mutation Taster		=96/4	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2273238;

hg19: chr6-90326360;

COSMIC: COSV60228845;

COSMIC: COSV60228845;