14-104938335-A-T

Position:

• chr14-104938335-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_138420.4(AHNAK2):​c.17116T>A​(p.Ser5706Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: AHNAK2 NM_138420.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.00

Genes affected

AHNAK2 (HGNC:20125): (AHNAK nucleoprotein 2) This gene encodes a large nucleoprotein. The encoded protein has a tripartite domain structure with a relatively short N-terminus and a long C-terminus, separated by a large body of repeats. The N-terminal PSD-95/Discs-large/ZO-1 (PDZ)-like domain is thought to function in the formation of stable homodimers. The encoded protein may play a role in calcium signaling by associating with calcium channel proteins. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2017]

AHNAK2 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14157867).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AHNAK2	NM_138420.4	c.17116T>A	p.Ser5706Thr	missense_variant	7/7	ENST00000333244.6	NP_612429.2
AHNAK2	NM_001350929.2	c.16816T>A	p.Ser5606Thr	missense_variant	7/7		NP_001337858.1
AHNAK2	XM_024449463.2	c.16816T>A	p.Ser5606Thr	missense_variant	7/7		XP_024305231.1
AHNAK2	XM_047430904.1	c.16816T>A	p.Ser5606Thr	missense_variant	7/7		XP_047286860.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AHNAK2	ENST00000333244.6	c.17116T>A	p.Ser5706Thr	missense_variant	7/7	5	NM_138420.4	ENSP00000353114.4
AHNAK2	ENST00000557457.1	c.2110T>A	p.Ser704Thr	missense_variant	3/3	1		ENSP00000450998.1
AHNAK2	ENST00000555122.1	n.17244T>A		non_coding_transcript_exon_variant	6/6	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 74

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 11, 2024

The c.17116T>A (p.S5706T) alteration is located in exon 7 (coding exon 7) of the AHNAK2 gene. This alteration results from a T to A substitution at nucleotide position 17116, causing the serine (S) at amino acid position 5706 to be replaced by a threonine (T). 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	0.15
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	21
DANN	Benign	0.87
DEOGEN2	Benign	0.031	.;T
Eigen	Uncertain	0.20
Eigen_PC	Benign	0.071
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.41	T;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.14	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	.;L
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-1.6	N;N
REVEL	Benign	0.080
Sift	Benign	0.37	T;D
Sift4G	Uncertain	0.020	D;D
Polyphen		0.99	.;D
Vest4		0.20
MutPred		0.22		.;Loss of phosphorylation at S5706 (P = 0.0403);
MVP		0.12
ClinPred		0.88	D
GERP RS		4.0
Varity_R		0.24
gMVP		0.016

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: chr14-105404672;