2-210044061-A-T

Variant names:

• chr2-210044061-A-T
• NM_152519.4:c.1799T>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_152519.4(KANSL1L):​c.1799T>A​(p.Met600Lys) 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. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: KANSL1L NM_152519.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.40
• Publications: 0 publications found

Genes affected

KANSL1L (HGNC:26310): (KAT8 regulatory NSL complex subunit 1 like) Predicted to enable histone acetyltransferase binding activity. Predicted to be part of NSL complex. [provided by Alliance of Genome Resources, Apr 2022]

KANSL1L-AS1 (HGNC:41139): (KANSL1L antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12581518).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152519.4. 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
	KANSL1L	NM_152519.4	MANE Select	c.1799T>A	p.Met600Lys	missense	Exon 7 of 15	NP_689732.2
	KANSL1L	NM_001307976.2		c.1799T>A	p.Met600Lys	missense	Exon 7 of 14	NP_001294905.1	A0AUZ9-2
	KANSL1L-AS1	NR_110291.1		n.969+8817A>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KANSL1L	ENST00000281772.14	TSL:5 MANE Select	c.1799T>A	p.Met600Lys	missense	Exon 7 of 15	ENSP00000281772.8	A0AUZ9-1
	KANSL1L	ENST00000418791.5	TSL:1	c.1799T>A	p.Met600Lys	missense	Exon 7 of 14	ENSP00000405724.1	A0AUZ9-2
	KANSL1L	ENST00000452086.5	TSL:1	c.1799T>A	p.Met600Lys	missense	Exon 7 of 8	ENSP00000401408.1	A0AUZ9-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.045	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	15
DANN	Benign	0.85
DEOGEN2	Benign	0.010	T
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.33
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.0040	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	L
PhyloP100		1.4
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.062
Sift	Benign	0.29	T
Sift4G	Benign	0.31	T
Polyphen		0.43	B
Vest4		0.47
MutPred		0.39		Gain of disorder (P = 0.0182)
MVP		0.055
MPC		0.099
ClinPred		0.30	T
GERP RS		2.5
Varity_R		0.15
gMVP		0.23
Mutation Taster		=88/12	polymorphism

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

Other links and lift over

hg19: chr2-210908785;