16-2528375-CC-GA

Variant names:

• chr16-2528375-CC-GA
• NM_001330449.2:c.857_858delCCinsGA
• AMDHD2 p.Pro286Arg

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_001330449.2(AMDHD2):​c.857_858delCCinsGA​(p.Pro286Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: AMDHD2 NM_001330449.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.69
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001330449.2. 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
	AMDHD2	NM_001330449.2	MANE Select	c.857_858delCCinsGA	p.Pro286Arg	missense	N/A	NP_001317378.1	Q9Y303-1
	AMDHD2	NM_001145815.2		c.857_858delCCinsGA	p.Pro286Arg	missense	N/A	NP_001139287.1	Q9Y303-3
	AMDHD2	NM_015944.4		c.857_858delCCinsGA	p.Pro286Arg	missense	N/A	NP_057028.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AMDHD2	ENST00000293971.11	TSL:1 MANE Select	c.857_858delCCinsGA	p.Pro286Arg	missense	N/A	ENSP00000293971.6	Q9Y303-1
	AMDHD2	ENST00000302956.8	TSL:1	c.857_858delCCinsGA	p.Pro286Arg	missense	N/A	ENSP00000307481.4	Q9Y303-2
	AMDHD2	ENST00000413459.7	TSL:2	c.857_858delCCinsGA	p.Pro286Arg	missense	N/A	ENSP00000391596.3	Q9Y303-3

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.7

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr16-2578376;