7-16610615-C-A

Variant names:

• chr7-16610615-C-A
• rs1403566645
• NM_020319.3:c.680G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_020319.3(ANKMY2):​c.680G>T​(p.Cys227Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,612 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C227S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ANKMY2 NM_020319.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.57
• Publications: 0 publications found

Genes affected

ANKMY2 (HGNC:25370): (ankyrin repeat and MYND domain containing 2) Predicted to enable enzyme binding activity and metal ion binding activity. Predicted to be located in cilium. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000287799 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020319.3. 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
	ANKMY2	NM_020319.3	MANE Select	c.680G>T	p.Cys227Phe	missense	Exon 6 of 10	NP_064715.1	Q8IV38

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKMY2	ENST00000306999.7	TSL:1 MANE Select	c.680G>T	p.Cys227Phe	missense	Exon 6 of 10	ENSP00000303570.2	Q8IV38
	ANKMY2	ENST00000949063.1		c.878G>T	p.Cys293Phe	missense	Exon 7 of 11	ENSP00000619122.1
	ANKMY2	ENST00000949062.1		c.761G>T	p.Cys254Phe	missense	Exon 7 of 11	ENSP00000619121.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461612 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727114

African (AFR) AF: 0.00 AC: 0 AN: 33466

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26122

East Asian (EAS) AF: 0.00 AC: 0 AN: 39650

South Asian (SAS) AF: 0.00 AC: 0 AN: 86242

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53402

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111870

Other (OTH) AF: 0.00 AC: 0 AN: 60380

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Pathogenic	0.37	D
BayesDel_noAF	Pathogenic	0.29
CADD	Uncertain	24
DANN	Benign	0.86
DEOGEN2	Benign	0.058	T
Eigen	Benign	0.053
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.032	D
MetaRNN	Uncertain	0.73	D
MetaSVM	Benign	-0.41	T
MutationAssessor	Benign	1.8	L
PhyloP100		7.6
PrimateAI	Uncertain	0.69	T
PROVEAN	Uncertain	-4.3	D
REVEL	Uncertain	0.52
Sift	Benign	0.72	T
Sift4G	Benign	0.75	T
Polyphen		0.042	B
Vest4		0.91
MutPred		0.59		Loss of helix (P = 0.0196)
MVP		0.82
MPC		0.066
ClinPred		0.96	D
GERP RS		5.9
Varity_R		0.53
gMVP		0.81
Mutation Taster		=41/59	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.26		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.26		Position offset: -11

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

Other links and lift over

dbSNP: rs1403566645; hg19: chr7-16650240;