2-127564190-A-G

Position:

• chr2-127564190-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 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. 13/21 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: MYO7B NM_001393586.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.57

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25918168).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYO7B	NM_001393586.1	c.56A>G	p.Lys19Arg	missense_variant	3/48	ENST00000409816.8
LOC105373609	NR_132317.1	n.182+498T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYO7B	ENST00000409816.8	c.56A>G	p.Lys19Arg	missense_variant	3/48	1	NM_001393586.1
MYO7B	ENST00000428314.5	c.56A>G	p.Lys19Arg	missense_variant	3/47	5		P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 29, 2021

The c.56A>G (p.K19R) alteration is located in exon 3 (coding exon 2) of the MYO7B gene. This alteration results from a A to G substitution at nucleotide position 56, causing the lysine (K) at amino acid position 19 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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;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;T
MetaSVM	Uncertain	0.26	D
MutationAssessor	Benign	1.8	L;L
MutationTaster	Benign	0.57	D;D;D
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-1.1	N;N
REVEL	Uncertain	0.39
Sift	Uncertain	0.014	D;D
Sift4G	Benign	0.064	T;T
Polyphen		0.87	P;P
Vest4		0.087
MutPred		0.42		Loss of methylation at K19 (P = 0.0144);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

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-128321765;