Variant 7-129225261-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_015328.4(AHCYL2):c.185T>G(p.Val62Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000015 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

AHCYL2
NM_015328.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0770

Variant links:

Genes affected

AHCYL2 (HGNC:22204): (adenosylhomocysteinase like 2) The protein encoded by this gene acts as a homotetramer and may be involved in the conversion of S-adenosyl-L-homocysteine to L-homocysteine and adenosine. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2011]

AHCYL2 links:

AHCYL2 (HGNC:):

AHCYL2 links:

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ACMG classification

Classification made for transcript

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=0.099059135).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AHCYL2	NM_015328.4 linkuse as main transcript	c.185T>G	p.Val62Gly	missense_variant	1/17	ENST00000325006.8	NP_056143.1	Q96HN2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AHCYL2	ENST00000325006.8 linkuse as main transcript	c.185T>G	p.Val62Gly	missense_variant	1/17	1	NM_015328.4	ENSP00000315931.3		Q96HN2-1
AHCYL2	ENST00000446544.6 linkuse as main transcript	c.185T>G	p.Val62Gly	missense_variant	1/17	1		ENSP00000413639.2		Q96HN2-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000154

AC:

AN:

1297312

Hom.:

Cov.:

AF XY:

0.00000313

AC XY:

AN XY:

639518

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000455

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:

9.60e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 13, 2021

The c.185T>G (p.V62G) alteration is located in exon 1 (coding exon 1) of the AHCYL2 gene. This alteration results from a T to G substitution at nucleotide position 185, causing the valine (V) at amino acid position 62 to be replaced by a glycine (G). 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

0.068

BayesDel_addAF

Uncertain

0.018

BayesDel_noAF

Benign

-0.21

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.088

T;.

Eigen

Benign

-0.72

Eigen_PC

Benign

-0.55

FATHMM_MKL

Benign

0.21

LIST_S2

Benign

0.13

T;T

M_CAP

Uncertain

0.26

MetaRNN

Benign

0.099

T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.34

N;N

PrimateAI

Pathogenic

0.91

PROVEAN

Benign

-0.48

N;N

REVEL

Benign

0.24

Sift

Uncertain

0.0050

D;D

Sift4G

Benign

0.28

T;T

Polyphen

0.0030

B;B

Vest4

0.23

MutPred

0.16

Loss of stability (P = 0.0569);Loss of stability (P = 0.0569);

MVP

0.17

MPC

1.1

ClinPred

0.67

GERP RS

3.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.11

gMVP

0.23

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over