Genetic Variant AMDHD2:p.Leu186Leu (chr16-2527913-C-T) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001330449.2(AMDHD2):c.556C>T(p.Leu186Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000969 in 1,596,964 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00054 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0010 ( 2 hom. )

Consequence

AMDHD2
NM_001330449.2 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.46

Variant links:

Genes affected

AMDHD2 (HGNC:24262): (amidohydrolase domain containing 2) Enables N-acetylglucosamine-6-phosphate deacetylase activity. Predicted to be involved in N-acetylglucosamine catabolic process. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

AMDHD2 links:

ENSG00000259784 (HGNC:):

ENSG00000259784 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.58).

BP6

Variant 16-2527913-C-T is Benign according to our data. Variant chr16-2527913-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2646064.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=2.46 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AMDHD2	NM_001330449.2 link	c.556C>T	p.Leu186Leu	synonymous_variant	Exon 5 of 11	ENST00000293971.11	NP_001317378.1	Q9Y303-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AMDHD2	ENST00000293971.11 link	c.556C>T	p.Leu186Leu	synonymous_variant	Exon 5 of 11	1	NM_001330449.2	ENSP00000293971.6		Q9Y303-1
ENSG00000259784	ENST00000569317.1 link	c.415C>T	p.Leu139Leu	synonymous_variant	Exon 4 of 4	3		ENSP00000455561.1		H3BQ15

Frequencies

GnomAD3 genomes

AF:

0.000545

AC:

AN:

152242

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000265

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000392

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000376

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000897

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000508

AC:

113

AN:

222456

Hom.:

AF XY:

0.000511

AC XY:

AN XY:

123252

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000358

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000173

Gnomad NFE exome

AF:

0.000977

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00101

AC:

1465

AN:

1444604

Hom.:

Cov.:

AF XY:

0.000999

AC XY:

718

AN XY:

719012

show subpopulations

Gnomad4 AFR exome

AF:

0.0000599

Gnomad4 AMR exome

AF:

0.000317

Gnomad4 ASJ exome

AF:

0.0000384

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000204

Gnomad4 NFE exome

AF:

0.00126

Gnomad4 OTH exome

AF:

0.000700

GnomAD4 genome

AF:

0.000545

AC:

AN:

152360

Hom.:

Cov.:

AF XY:

0.000550

AC XY:

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.000264

Gnomad4 AMR

AF:

0.000392

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000376

Gnomad4 NFE

AF:

0.000897

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000784

Hom.:

Bravo

AF:

0.000533

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jun 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

AMDHD2: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

7.3

DANN

Benign

0.85

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over