2-210023094-A-G

Variant names:

• chr2-210023094-A-G
• rs1387292190
• NM_152519.4:c.2819T>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_152519.4(KANSL1L):​c.2819T>C​(p.Val940Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000132 in 151,876 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V940D) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.000013 (0 hom., cov: 32)
• Consequence: KANSL1L NM_152519.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.912
• 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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.029097289).

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.2819T>C	p.Val940Ala	missense	Exon 15 of 15	NP_689732.2
	KANSL1L	NM_001307976.2		c.2693T>C	p.Val898Ala	missense	Exon 14 of 14	NP_001294905.1	A0AUZ9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KANSL1L	ENST00000281772.14	TSL:5 MANE Select	c.2819T>C	p.Val940Ala	missense	Exon 15 of 15	ENSP00000281772.8	A0AUZ9-1
	KANSL1L	ENST00000418791.5	TSL:1	c.2693T>C	p.Val898Ala	missense	Exon 14 of 14	ENSP00000405724.1	A0AUZ9-2
	KANSL1L	ENST00000867426.1		c.2819T>C	p.Val940Ala	missense	Exon 15 of 15	ENSP00000537485.1

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 151876 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 151876 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74168

African (AFR) AF: 0.00 AC: 0 AN: 41330

American (AMR) AF: 0.00 AC: 0 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4806

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10580

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 67958

Other (OTH) AF: 0.00 AC: 0 AN: 2088

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	0.88
DANN	Benign	0.63
DEOGEN2	Benign	0.0033	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0097	N
LIST_S2	Benign	0.29	T
M_CAP	Benign	0.0041	T
MetaRNN	Benign	0.029	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	L
PhyloP100		-0.91
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.10	N
REVEL	Benign	0.016
Sift	Benign	0.21	T
Sift4G	Benign	0.40	T
Polyphen		0.038	B
Vest4		0.019
MutPred		0.096		Gain of relative solvent accessibility (P = 0.0249)
MVP		0.061
MPC		0.079
ClinPred		0.11	T
GERP RS		-3.8
Varity_R		0.015
gMVP		0.059
Mutation Taster		=99/1	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

dbSNP: rs1387292190; hg19: chr2-210887818;