2-127559727-C-T

Variant names:

• chr2-127559727-C-T
• rs776160939
• NM_001393586.1:c.5C>T

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.5C>T​(p.Ser2Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000452 in 1,613,730 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000048 (0 hom.)
• Consequence: MYO7B NM_001393586.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.234
• Publications: 3 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]

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=0.07981652).

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.5C>T	p.Ser2Leu	missense	Exon 2 of 48	NP_001380515.1	A0A8C8KL71
	MYO7B	NM_001080527.2		c.5C>T	p.Ser2Leu	missense	Exon 2 of 47	NP_001073996.1	Q6PIF6-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO7B	ENST00000409816.8	TSL:1 MANE Select	c.5C>T	p.Ser2Leu	missense	Exon 2 of 48	ENSP00000386461.3	A0A8C8KL71
	MYO7B	ENST00000897059.1		c.5C>T	p.Ser2Leu	missense	Exon 2 of 48	ENSP00000567118.1
	MYO7B	ENST00000428314.5	TSL:5	c.5C>T	p.Ser2Leu	missense	Exon 2 of 47	ENSP00000415090.1	Q6PIF6-1

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152052 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

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

GnomAD2 exomes AF: 0.0000201 AC: 5 AN: 249258 AF XY: 0.0000370

Gnomad AFR exome AF: 0.0000646

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000354

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000479 AC: 70 AN: 1461678 Hom.: 0 Cov.: 30 AF XY: 0.0000468 AC XY: 34 AN XY: 727122

African (AFR) AF: 0.0000597 AC: 2 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53400

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000585 AC: 65 AN: 1111852

Other (OTH) AF: 0.0000497 AC: 3 AN: 60372

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152052 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74262

African (AFR) AF: 0.0000242 AC: 1 AN: 41376

American (AMR) AF: 0.00 AC: 0 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10592

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

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68028

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

Alfa AF: 0.0000251 Hom.: 0

Bravo AF: 0.0000378

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ExAC AF: 0.0000165 AC: 2

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	0.11
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	15
DANN	Benign	0.90
DEOGEN2	Benign	0.0052	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.080	T
MetaSVM	Benign	-0.75	T
MutationAssessor	Benign	0.69	N
PhyloP100		0.23
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-0.39	N
REVEL	Benign	0.093
Sift	Benign	0.13	T
Sift4G	Uncertain	0.029	D
Polyphen		0.020	B
Vest4		0.21
MutPred		0.35		Gain of stability (P = 0.0061)
MVP		0.27
MPC		0.070
ClinPred		0.020	T
GERP RS		2.0
Varity_R		0.036
gMVP		0.27
Mutation Taster		=93/7	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		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: rs776160939; hg19: chr2-128317302; COSMIC: COSV67347248;