rs61744890

Variant names:

• chr6-89606057-A-G
• rs61744890
• NM_001242809.2:c.369A>G

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_001242809.2(ANKRD6):​c.369A>G​(p.Ser123Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00108 in 1,595,724 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0058 (11 hom., cov: 32)
  • Exomes 𝑓: 0.00058 (7 hom.)
• Consequence: ANKRD6 NM_001242809.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0620
• Publications: 0 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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP6: Variant 6-89606057-A-G is Benign according to our data. Variant chr6-89606057-A-G is described in ClinVar as Benign. ClinVar VariationId is 784092.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.062 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00579 (881/152290) while in subpopulation AFR AF = 0.0204 (847/41556). AF 95% confidence interval is 0.0192. There are 11 homozygotes in GnomAd4. There are 422 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 11 AR gene

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.369A>G	p.Ser123Ser	synonymous	Exon 5 of 16	NP_001229738.1	Q9Y2G4-2
	ANKRD6	NM_001242811.1		c.369A>G	p.Ser123Ser	synonymous	Exon 5 of 16	NP_001229740.1	Q9Y2G4-2
	ANKRD6	NM_014942.4		c.369A>G	p.Ser123Ser	synonymous	Exon 5 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.369A>G	p.Ser123Ser	synonymous	Exon 5 of 16	ENSP00000345767.4	Q9Y2G4-2
	ANKRD6	ENST00000447838.6	TSL:1	c.369A>G	p.Ser123Ser	synonymous	Exon 5 of 16	ENSP00000396771.2	Q9Y2G4-3
	ANKRD6	ENST00000369408.9	TSL:1	c.369A>G	p.Ser123Ser	synonymous	Exon 5 of 15	ENSP00000358416.5	Q9Y2G4-1

Frequencies

GnomAD3 genomes AF: 0.00579 AC: 881 AN: 152172 Hom.: 11 Cov.: 32

Gnomad AFR AF: 0.0204

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00157

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00430

GnomAD2 exomes AF: 0.00144 AC: 321 AN: 222358 AF XY: 0.00113

Gnomad AFR exome AF: 0.0218

Gnomad AMR exome AF: 0.000726

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000120

Gnomad OTH exome AF: 0.000181

GnomAD4 exome AF: 0.000583 AC: 842 AN: 1443434 Hom.: 7 Cov.: 28 AF XY: 0.000492 AC XY: 352 AN XY: 715978

African (AFR) AF: 0.0215 AC: 714 AN: 33180

American (AMR) AF: 0.00101 AC: 43 AN: 42554

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25684

East Asian (EAS) AF: 0.00 AC: 0 AN: 39094

South Asian (SAS) AF: 0.00 AC: 0 AN: 82258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52350

Middle Eastern (MID) AF: 0.000698 AC: 4 AN: 5730

European-Non Finnish (NFE) AF: 0.0000290 AC: 32 AN: 1102866

Other (OTH) AF: 0.000821 AC: 49 AN: 59718

GnomAD4 genome AF: 0.00579 AC: 881 AN: 152290 Hom.: 11 Cov.: 32 AF XY: 0.00567 AC XY: 422 AN XY: 74470

African (AFR) AF: 0.0204 AC: 847 AN: 41556

American (AMR) AF: 0.00157 AC: 24 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68020

Other (OTH) AF: 0.00426 AC: 9 AN: 2114

Alfa AF: 0.00289 Hom.: 2

Bravo AF: 0.00696

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	5.9
DANN	Benign	0.69
PhyloP100		-0.062
Mutation Taster		=97/3	polymorphism

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: rs61744890; hg19: chr6-90315776;