chr2-127564190-A-G

Variant names:

• chr2-127564190-A-G
• NM_001393586.1:c.56A>G

Variant summary

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

The NM_001393586.1(MYO7B):​c.56A>G​(p.Lys19Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 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: MYO7B NM_001393586.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.57
• Publications: 0 publications found

Genes affected

MYO7B (HGNC:7607): (myosin VIIB) The protein encoded by this gene is found in brush border microvilli of epithelial cells in the intestines and kidneys. The encoded protein is involved in linking protocadherins to the actin cytoskeleton and is essential for proper microvilli function. This protein aids in the accumulation of intermicrovillar adhesion components such as harmonin and ANKS4B, and this accumulation is necessary for normal brush border action. [provided by RefSeq, Jan 2017]

LOC105373609 (HGNC:):

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=0.25918168).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001393586.1. 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
	MYO7B	NM_001393586.1	MANE Select	c.56A>G	p.Lys19Arg	missense	Exon 3 of 48	NP_001380515.1	A0A8C8KL71
	MYO7B	NM_001080527.2		c.56A>G	p.Lys19Arg	missense	Exon 3 of 47	NP_001073996.1	Q6PIF6-1
	LOC105373609	NR_132317.1		n.182+498T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO7B	ENST00000409816.8	TSL:1 MANE Select	c.56A>G	p.Lys19Arg	missense	Exon 3 of 48	ENSP00000386461.3	A0A8C8KL71
	MYO7B	ENST00000897059.1		c.56A>G	p.Lys19Arg	missense	Exon 3 of 48	ENSP00000567118.1
	MYO7B	ENST00000428314.5	TSL:5	c.56A>G	p.Lys19Arg	missense	Exon 3 of 47	ENSP00000415090.1	Q6PIF6-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

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	0.072
BayesDel_addAF	Benign	-0.011	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0041	T
Eigen	Benign	0.12
Eigen_PC	Benign	0.14
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.061	D
MetaRNN	Benign	0.26	T
MetaSVM	Uncertain	0.26	D
MutationAssessor	Benign	1.8	L
PhyloP100		6.6
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-1.1	N
REVEL	Uncertain	0.39
Sift	Uncertain	0.014	D
Sift4G	Benign	0.064	T
Polyphen		0.87	P
Vest4		0.087
MutPred		0.42		Loss of methylation at K19 (P = 0.0144)
MVP		0.66
MPC		0.15
ClinPred		0.89	D
GERP RS		5.5
Varity_R		0.15
gMVP		0.29
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: chr2-128321765;