6-89630468-G-A

Variant names:

• chr6-89630468-G-A
• rs9362667
• NM_001242809.2:c.1648G>A

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.1648G>A​(p.Ala550Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00468 in 1,613,662 control chromosomes in the GnomAD database, including 245 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 0.0061 (24 hom., cov: 33)
  • Exomes 𝑓: 0.0045 (221 hom.)
• Consequence: ANKRD6 NM_001242809.2 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.907
• Publications: 7 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)

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0019686222).
• BP6: Variant 6-89630468-G-A is Benign according to our data. Variant chr6-89630468-G-A is described in ClinVar as Benign. ClinVar VariationId is 3058841.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0852 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.1648G>A	p.Ala550Thr	missense	Exon 16 of 16	NP_001229738.1
	ANKRD6	NM_001242811.1		c.1648G>A	p.Ala550Thr	missense	Exon 16 of 16	NP_001229740.1
	ANKRD6	NM_014942.4		c.1633G>A	p.Ala545Thr	missense	Exon 16 of 16	NP_055757.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKRD6	ENST00000339746.9	TSL:1 MANE Select	c.1648G>A	p.Ala550Thr	missense	Exon 16 of 16	ENSP00000345767.4
	ANKRD6	ENST00000447838.6	TSL:1	c.1633G>A	p.Ala545Thr	missense	Exon 16 of 16	ENSP00000396771.2
	ANKRD6	ENST00000369408.9	TSL:1	c.1543G>A	p.Ala515Thr	missense	Exon 15 of 15	ENSP00000358416.5

Frequencies

GnomAD3 genomes AF: 0.00609 AC: 927 AN: 152216 Hom.: 24 Cov.: 33

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000589

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.0924

Gnomad SAS AF: 0.00476

Gnomad FIN AF: 0.0323

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000882

Gnomad OTH AF: 0.00335

GnomAD2 exomes AF: 0.0103 AC: 2551 AN: 248558 AF XY: 0.00986

Gnomad AFR exome AF: 0.000323

Gnomad AMR exome AF: 0.0000871

Gnomad ASJ exome AF: 0.000200

Gnomad EAS exome AF: 0.0934

Gnomad FIN exome AF: 0.0281

Gnomad NFE exome AF: 0.00132

Gnomad OTH exome AF: 0.00597

GnomAD4 exome AF: 0.00453 AC: 6627 AN: 1461328 Hom.: 221 Cov.: 29 AF XY: 0.00460 AC XY: 3343 AN XY: 726954

African (AFR) AF: 0.000269 AC: 9 AN: 33464

American (AMR) AF: 0.000134 AC: 6 AN: 44662

Ashkenazi Jewish (ASJ) AF: 0.000268 AC: 7 AN: 26084

East Asian (EAS) AF: 0.0971 AC: 3855 AN: 39700

South Asian (SAS) AF: 0.00282 AC: 243 AN: 86246

European-Finnish (FIN) AF: 0.0262 AC: 1397 AN: 53382

Middle Eastern (MID) AF: 0.000520 AC: 3 AN: 5768

European-Non Finnish (NFE) AF: 0.000592 AC: 658 AN: 1111682

Other (OTH) AF: 0.00744 AC: 449 AN: 60340

GnomAD4 genome AF: 0.00606 AC: 923 AN: 152334 Hom.: 24 Cov.: 33 AF XY: 0.00799 AC XY: 595 AN XY: 74504

African (AFR) AF: 0.0000962 AC: 4 AN: 41582

American (AMR) AF: 0.000588 AC: 9 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3472

East Asian (EAS) AF: 0.0920 AC: 477 AN: 5184

South Asian (SAS) AF: 0.00476 AC: 23 AN: 4832

European-Finnish (FIN) AF: 0.0323 AC: 343 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000882 AC: 60 AN: 68030

Other (OTH) AF: 0.00284 AC: 6 AN: 2114

Alfa AF: 0.00358 Hom.: 58

Bravo AF: 0.00484

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.000250 AC: 1

ESP6500EA AF: 0.000598 AC: 5

ExAC AF: 0.0101 AC: 1228

Asia WGS AF: 0.0330 AC: 117 AN: 3478

EpiCase AF: 0.000654

EpiControl AF: 0.000296

ClinVar

ClinVar submissions as Germline

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	0.074
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	20
DANN	Benign	0.49
DEOGEN2	Benign	0.013	T
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.30
FATHMM_MKL	Benign	0.33	N
LIST_S2	Benign	0.80	T
MetaRNN	Benign	0.0020	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.34	N
PhyloP100		0.91
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.74	N
REVEL	Benign	0.11
Sift	Benign	0.20	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.057
MPC		0.050
ClinPred		0.0034	T
GERP RS		4.2
Varity_R		0.052
gMVP		0.14
Mutation Taster		=94/6	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: rs9362667; hg19: chr6-90340187; COSMIC: COSV60231777; COSMIC: COSV60231777;