7-16615769-G-T

Variant names:

• chr7-16615769-G-T
• NM_020319.3:c.506C>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_020319.3(ANKMY2):​c.506C>A​(p.Thr169Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,890 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ANKMY2 NM_020319.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.37

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKMY2	NM_020319.3	c.506C>A	p.Thr169Asn	missense_variant	Exon 5 of 10	ENST00000306999.7	NP_064715.1
LOC105375169	XR_007060225.1	n.222-257G>T		intron_variant	Intron 2 of 4
LOC105375169	XR_007060226.1	n.222-257G>T		intron_variant	Intron 2 of 4
LOC105375169	XR_007060227.1	n.81-257G>T		intron_variant	Intron 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANKMY2	ENST00000306999.7	c.506C>A	p.Thr169Asn	missense_variant	Exon 5 of 10	1	NM_020319.3	ENSP00000303570.2
ANKMY2	ENST00000628652.1	c.506C>A	p.Thr169Asn	missense_variant	Exon 5 of 9	5		ENSP00000485738.1
ANKMY2	ENST00000447802.3	n.506C>A		non_coding_transcript_exon_variant	Exon 5 of 11	2		ENSP00000392259.1
ENSG00000287799	ENST00000663260.1	n.358-257G>T		intron_variant	Intron 3 of 3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461890 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727244

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 22, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.506C>A (p.T169N) alteration is located in exon 5 (coding exon 5) of the ANKMY2 gene. This alteration results from a C to A substitution at nucleotide position 506, causing the threonine (T) at amino acid position 169 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Uncertain	0.027	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.021	T;.
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.91	D;D
M_CAP	Benign	0.024	T
MetaRNN	Uncertain	0.64	D;D
MetaSVM	Benign	-0.66	T
MutationAssessor	Benign	2.0	M;.
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-2.4	N;.
REVEL	Benign	0.26
Sift	Uncertain	0.018	D;.
Sift4G	Uncertain	0.049	D;D
Polyphen		0.93	P;.
Vest4		0.69
MutPred		0.38		Loss of catalytic residue at T169 (P = 0.0043);Loss of catalytic residue at T169 (P = 0.0043);
MVP		0.72
MPC		0.053
ClinPred		0.95	D
GERP RS		5.7
Varity_R		0.47
gMVP		0.50

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-16655394;